Back to resultsStudy of Niraparib, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy in Combination With TSR-042
Primary Purpose
Neoplasms, Metastatic Cancer, Advanced Cancer
Status
Active
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Niraparib
TSR-042
Carboplatin-Paclitaxel
Bevacizumab
TSR-022
Carboplatin-Pemetrexed
Carboplatin-Nab-Paclitaxel
Sponsored by
About this trial
This is an interventional treatment trial for Neoplasms
Eligibility Criteria
Inclusion Criteria:
- Patient has histologically or cytologically proven advanced (unresectable) or metastatic cancer as outlined below according to study part and disease type:
- Part A: Patients with previously treated advanced or metastatic cancer. Patient may have received no more than 4 lines of treatment for advanced or metastatic cancer. Hormonal treatment will not be considered a prior line of treatment.
- Part B: Patients with advanced or metastatic cancer for which treatment with carboplatin-paclitaxel is considered appropriate therapy. Patient may have received no more than 1 prior line of chemotherapy in the metastatic setting. Hormonal treatment will not be considered a prior line of treatment.
- Part C: Patients with previously treated advanced or metastatic cancer. Patient may have received no more than 4 lines of treatment for advanced or metastatic cancer. Hormonal treatment will not be considered a prior line of treatment.
- Part D: Patients in whom carboplatin-paclitaxel and bevacizumab is considered appropriate therapy. Patient may have received no more than 1 prior line of chemotherapy in the metastatic setting. Hormonal treatment will not be considered a prior line of treatment.
- Part E and F: Patients who have not received prior systemic therapy, including targeted therapy and biologic agents, for their advanced or metastatic (Stage ≥ IIIB or IV) Non-Squamous NSCLC. Patients who have received neoadjuvant or adjuvant therapy are eligible as long as development of advanced or metastatic disease occurred at least 12 months after completion of neoadjuvant or adjuvant therapy.
- Part G, H, and I: Patients who have not received prior systemic therapy, including targeted therapy and biologic agents, for their advanced or metastatic (Stage ≥ IIIB or IV) NSCLC. Patients who have received neoadjuvant or adjuvant therapy are eligible as long as development of advanced or metastatic disease occurred at least 12 months after completion of neoadjuvant or adjuvant therapy.
- Patient has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
- Patient has adequate organ function.
- Female patient has a negative serum pregnancy test within 72 hours prior to taking study treatment if of childbearing potential and agrees to abstain from activities that could result in pregnancy from screening through 180 days after the last dose of study treatment, or is of non-childbearing potential.
- Male patient agrees to use an adequate method of contraception and not donate sperm starting with the first dose of study treatment through 90 days after the last dose of study treatment. Note: Abstinence is acceptable if this is the established and preferred contraception for the patient.
- Patient has measurable lesions by RECIST v1.1.
For Part A and C, in addition to the general inclusion criteria, patients must also meet the following additional criterion to be considered eligible to participate in this study:
- Patient is able to take oral medications.
- For patients to be eligible for any parts of the study using niraparib 300 mg as a starting dose, a screening actual body weight ≥ 77 kg and screening platelet count ≥ 150,000 u/L is necessary.
Exclusion Criteria: (Patients will not be eligible for the study entry if any of the following criteria are met)
- Patient has known active central nervous system metastases, carcinomatous meningitis, or both.
- Patient has a known additional malignancy that progressed or required active treatment within the last 2 years. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin that has undergone potentially curative therapy, or in situ cervical cancer.
- Patient is considered a poor medical risk due to a serious, uncontrolled medical disorder, nonmalignant systemic disease, or active infection that requires systemic therapy.
- Patient has a condition (such as transfusion-dependent anemia or thrombocytopenia), therapy, or laboratory abnormality that might confound the study results or interfere with the patient's participation
- Patient is pregnant or expecting to conceive children within the projected duration of the study, starting with the screening visit through 180 days after the last dose of study treatment.
Note: No data are available regarding the presence of niraparib or its metabolites in human milk, or on its effects on the breastfed infant or milk production. Because of the potential for serious adverse reactions in breastfed infants from niraparib, female patients should not breastfeed during treatment with niraparib and for 1 month after receiving the final dose.
- Patient has a known history of human immunodeficiency virus (type 1 or 2 antibodies).
- Patient has known active hepatitis B or hepatitis C.
- Patient has an active autoimmune disease that has required systemic treatment in the past 2 years.
- Patient has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 including ipilimumab), or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways.
- Patient has undergone prior treatment with a known PARP inhibitor.
- Known history or current diagnosis of MDS or AML.
- Patient has a known hypersensitivity to TSR-042 components or excipients.
For Parts B, D, E, F, G, H, and I, patients will not be eligible for study entry if any of the following additional exclusion criterion are met:
• Patient has a known hypersensitivity to any of the following relevant study treatments: carboplatin, paclitaxel, pemetrexed, nab-paclitaxel, or TSR-022 components or excipients.
For Parts C and D only, patients will not be eligible for study entry if the following additional exclusion criterion is met:
- Patient has clinically significant cardiovascular disease (e.g., significant cardiac conduction abnormalities, uncontrolled hypertension, myocardial infarction, cardiac arrhythmia or unstable angina, New York Heart Association Grade 2 or greater congestive heart failure, serious cardiac arrhythmia requiring medication, Grade 2 or greater peripheral vascular disease, and history of cerebrovascular accident [CVA]) within 6 months of enrollment.
- Patient has a history of bowel obstruction, including subocclusive disease, related to the underlying disease and history of abdominal fistula, gastrointestinal perforation, or intra abdominal abscesses. Evidence of recto-sigmoid involvement by pelvic examination or bowel involvement on CT scan or clinical symptoms of bowel obstruction.
- Patient has proteinuria as demonstrated by urine protein: creatinine ratio ≥1.0 at screening or urine dipstick for proteinuria ≥2 (patients discovered to have ≥2 proteinuria on dipstick at baseline should undergo 24-hour urine collection and must demonstrate <2 g of protein in 24 hours to be eligible).
- Patient is at increased bleeding risk due to concurrent conditions (e.g., major injuries or surgery within the past 28 days prior to start of study treatment, history of hemorrhagic stroke, transient ischemic attack, subarachnoid hemorrhage, or clinically significant hemorrhage within the past 3 months).
- Patient has a known hypersensitivity to bevacizumab components or excipients.
For Parts E and F only, patients will not be eligible for study entry if any of the following additional exclusion criteria are met:
- Patient is unable to interrupt aspirin or other nonsteroidal ant-inflammatory drugs, other than an aspirin dose ≤ 1.3 g per day, for a 5-day period (8-day period for long -acting agents, such as piroxicam.
- Patient is unable or unwilling to take folic acid, vitamin B12 supplement.
- Patient has symptomatic ascites or pleural effusion. A patient who is clinically stable following treatment for these conditions (including therapeutic thoraco- or paracentesis) is eligible.
For Parts G, H, and I only, patients will not be eligible for study entry if any of the following additional exclusion criteria are met:
• Patient has pre-existing peripheral neuropathy that is Grade ≥ 2 by Common Terminology Criteria for Adverse Events (CTCAE) version 4 criteria.
For Parts E, F, G, H and I only, patients will not be eligible for study entry if any of the following additional exclusion criteria are met:
• Patient has interstitial lung disease or a history of pneumonitis that required oral or intravenous glucocorticoids to assist with management.
Sites / Locations
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Arm 7
Arm 8
Arm 9
Arm 10
Arm 11
Arm Type
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Arm Label
Part A: TSR-042 and niraparib 200 mg QD
Part A: TSR-042 and niraparib 300 mg QD
Part B: TSR-042 and carboplatin-paclitaxel
Part C: TSR-042, niraparib 200 mg QD and bevacizumab
Part C: TSR-042, niraparib 300 mg QD and bevacizumab
Part D: TSR-042, carboplatin-paclitaxel and bevacizumab
Part E: TSR-042 and carboplatin-pemetrexed
Part F: TSR-042, TSR-022, and carboplatin-pemetrexed
Part G: TSR-042 and carboplatin-nab-paclitaxel
Part H: TSR-042, TSR-022, and carboplatin-nab-paclitaxel
Part I: TSR-042, TSR-022, and carboplatin-paclitaxel
Arm Description
Patients will receive TSR-042 500 milligram (mg), intravenous (IV) infusion on Day 1 of every cycle (every 3 weeks [Q3W]) for 4 cycles (each cycle is 21 days); followed by TSR-042 1000 mg, IV infusion on Day 1 of every other cycle (every 6 weeks [Q6W]) beginning on Day 1 of Cycle 5 along with niraparib 200 mg, once daily (QD), orally on Days 1 to 21 repeated Q3W.
Patients will receive TSR-042 500 mg, IV infusion on Day 1 of every cycle (Q3W) for 4 cycles (each cycle is 21 days); followed by TSR-042 1000 mg, IV infusion on Day 1 of every other cycle (Q6W) beginning on Day 1 of Cycle 5 along with niraparib 300 mg, QD, orally on Days 1 to 21 repeated Q3W.
Patients will receive TSR-042 500 mg, IV infusion on Day 1 of every cycle (Q3W) for 4 cycles (each cycle is 21 days); followed by TSR-042 1000 mg, IV infusion on Day 1 of every other cycle (Q6W) beginning on Day 1 of Cycle 5 along with carboplatin, IV infusion on Day 1 Q3W and paclitaxel 175 milligram per square meter (mg/m^2), IV infusion on Day 1 Q3W administered for 4 to 6 cycles.
Patients will receive TSR-042 500 mg, IV infusion on Day 1 of every cycle (Q3W) for 4 cycles (each cycle is 21 days); followed by TSR-042 1000 mg, IV infusion on Day 1 of every other cycle (Q6W) beginning on Day 1 of Cycle 5 along with niraparib 200 mg administered orally on Days 1 to 21 repeated Q3W and bevacizumab 15 mg/kilogram (kg), IV infusion on Day 1 of every 21-day cycle Q3W for up to 15 months.
Patients will receive TSR-042 500 mg, IV infusion on Day 1 of every cycle (Q3W) for 4 cycles (each cycle is 21 days); followed by TSR-042 1000 mg, IV infusion on Day 1 of every other cycle (Q6W) beginning on Day 1 of Cycle 5 along with niraparib 300 mg administered orally on Days 1 to 21 repeated Q3W and bevacizumab 15 mg/kg, IV infusion on Day 1 of every 21-day cycle Q3W for up to 15 months.
Patients will receive TSR-042 500 mg, IV infusion on Day 1 of every cycle (Q3W) for 4 cycles (each cycle is 21 days); followed by TSR-042 1000 mg, IV infusion on Day 1 of every other cycle (Q6W) beginning on Day 1 of Cycle 5 along with carboplatin, IV infusion on Day 1 Q3W and paclitaxel 175 mg/m^2, IV infusion on Day 1 Q3W administered for 4 to 6 cycles; and bevacizumab 15 mg/kg, IV infusion on Day 1 of every 21-day cycle Q3W for up to 15 months.
Patients will receive TSR-042 500 mg, IV infusion on Day 1 of every cycle (Q3W) along with carboplatin, IV infusion on Day 1 Q3W and pemetrexed 500 mg/m^2, IV infusion on Day 1 Q3W (with vitamin supplementation) administered for 6 cycles (each cycle is 21 days).
Patients will receive TSR-042 500 mg, IV infusion on Day 1 of every cycle (Q3W); and TSR-022 900 mg, IV infusion on Day 1 Q3W along with carboplatin, IV infusion on Day 1 Q3W administered for 5 cycles (each cycle is 21 days); and pemetrexed 500 mg/m^2, IV infusion on Day 1 Q3W (with vitamin supplementation).
Patients will receive TSR-042 500 mg, IV infusion on Day 1 of every cycle (Q3W) along with carboplatin, IV infusion on Day 1 Q3W for 4 to 6 cycles (each cycle is 21 days) and nab-paclitaxel 100 mg/m^2, IV infusion on Days 1, 8 and 15 (every week [Q1W]) of every 3 week cycle for 4 to 6 cycles.
Patients will receive TSR-042 500 mg, IV infusion on Day 1 of every cycle (Q3W); followed by TSR-022 900 mg, IV infusion on Day 1 Q3W along with carboplatin, IV infusion on Day 1 Q3W for 4 to 6 cycles (each cycle is 21 days) and nab-paclitaxel 100 mg/m^2, IV infusion on Days 1, 8 and 15 (Q1W) of every 3 week cycle for 4 to 6 cycles.
Patients will receive TSR-042 500 mg, IV infusion on Day 1 of every cycle (Q3W); followed by TSR-022 900 mg, IV infusion on Day 1 Q3W along with carboplatin, IV infusion on Day 1 Q3W and paclitaxel 175 mg/m^2, IV infusion on Day 1 Q3W for 4 to 6 cycles (each cycle is 21 days).
Outcomes
Primary Outcome Measures
Part A: Number of Participants With Dose-limiting Toxicity (DLT)
An event was considered a DLT if it occurred within the first 21 days of treatment, and met one of following DLT criteria:hematologic toxicity- Grade4 thrombocytopenia persists for >=7 days from the time of adverse event(AE) onset, Grade 4 neutropenia, Grade 4 or Grade 3 febrile neutropenia persists for >=7 days, Grade4 or Grade3 anemia requiring blood transfusion, Grade 3 thrombocytopenia associated with clinically significant bleeding, Grade 3 neutropenia associated with infection as described in Common Terminology Criteria for Adverse Events (CTCAE) version 4.0, drug related Grade 3 or 4 non-hematologic toxicity, drug related Grade 3 or 4 nonhematologic laboratory abnormality if any of the following also occur: abnormality leads to hospitalization and abnormality persists for >=7 days from the time of AE onset; drug related toxicity leading to prolonged delay (>2 weeks) in initiating Cycle 2. DLTs were collected during first cycle to establish recommended phase 2 dose (RP2D).
Part B: Number of Participants With DLT
An event was considered a DLT if it occurred within the first 21 days of treatment, and met one of following DLT criteria:hematologic toxicity- Grade4 thrombocytopenia persists for >=7 days from the time of AE onset, Grade 4 neutropenia, Grade 4 or Grade 3 febrile neutropenia persists for >=7 days, Grade4 or Grade3 anemia requiring blood transfusion, Grade 3 thrombocytopenia associated with clinically significant bleeding, Grade 3 neutropenia associated with infection as described in CTCAE version 4.0, drug related Grade 3 or 4 non-hematologic toxicity, drug related Grade 3 or 4 nonhematologic laboratory abnormality if any of the following also occur: abnormality leads to hospitalization and abnormality persists for >=7 days from the time of AE onset; drug related toxicity leading to prolonged delay (>2 weeks) in initiating Cycle 2. DLTs were collected during first cycle to establish RP2D.
Part C: Number of Participants With DLT
An event was considered a DLT if it occurred within the first 21 days of treatment, and met one of following DLT criteria:hematologic toxicity- Grade4 thrombocytopenia persists for >=7 days from the time of AE onset, Grade 4 neutropenia, Grade 4 or Grade 3 febrile neutropenia persists for >=7 days, Grade4 or Grade3 anemia requiring blood transfusion, Grade 3 thrombocytopenia associated with clinically significant bleeding, Grade 3 neutropenia associated with infection as described in CTCAE version 4.0, drug related Grade 3 or 4 non-hematologic toxicity, drug related Grade 3 or 4 nonhematologic laboratory abnormality if any of the following also occur: abnormality leads to hospitalization and abnormality persists for >=7 days from the time of AE onset; drug related toxicity leading to prolonged delay (>2 weeks) in initiating Cycle 2. DLTs were collected during first cycle to establish RP2D.
Part D: Number of Participants With DLT
An event was considered a DLT if it occurred within the first 21 days of treatment, and met one of following DLT criteria:hematologic toxicity- Grade4 thrombocytopenia persists for >=7 days from the time of AE onset, Grade 4 neutropenia, Grade 4 or Grade 3 febrile neutropenia persists for >=7 days, Grade4 or Grade3 anemia requiring blood transfusion, Grade 3 thrombocytopenia associated with clinically significant bleeding, Grade 3 neutropenia associated with infection as described in CTCAE version 4.0, drug related Grade 3 or 4 non-hematologic toxicity, drug related Grade 3 or 4 nonhematologic laboratory abnormality if any of the following also occur: abnormality leads to hospitalization and abnormality persists for >=7 days from the time of AE onset; drug related toxicity leading to prolonged delay (>2 weeks) in initiating Cycle 2. DLTs were collected during first cycle to establish RP2D.
Part E: Number of Participants With DLT
An event was considered a DLT if it occurred within the first 21 days of treatment, and met one of following DLT criteria:hematologic toxicity- Grade4 thrombocytopenia persists for >=7 days from the time of AE onset, Grade 4 neutropenia, Grade 4 or Grade 3 febrile neutropenia persists for >=7 days, Grade4 or Grade3 anemia requiring blood transfusion, Grade 3 thrombocytopenia associated with clinically significant bleeding, Grade 3 neutropenia associated with infection as described in CTCAE version 4.0, drug related Grade 3 or 4 non-hematologic toxicity, drug related Grade 3 or 4 nonhematologic laboratory abnormality if any of the following also occur: abnormality leads to hospitalization and abnormality persists for >=7 days from the time of AE onset; drug related toxicity leading to prolonged delay (>2 weeks) in initiating Cycle 2. DLTs were collected during first cycle to establish RP2D.
Part F: Number of Participants With DLT
An event was considered a DLT if it occurred within the first 21 days of treatment, and met one of following DLT criteria:hematologic toxicity- Grade4 thrombocytopenia persists for >=7 days from the time of AE onset, Grade 4 neutropenia, Grade 4 or Grade 3 febrile neutropenia persists for >=7 days, Grade4 or Grade3 anemia requiring blood transfusion, Grade 3 thrombocytopenia associated with clinically significant bleeding, Grade 3 neutropenia associated with infection as described in CTCAE version 4.0, drug related Grade 3 or 4 non-hematologic toxicity, drug related Grade 3 or 4 nonhematologic laboratory abnormality if any of the following also occur: abnormality leads to hospitalization and abnormality persists for >=7 days from the time of AE onset; drug related toxicity leading to prolonged delay (>2 weeks) in initiating Cycle 2. DLTs were collected during first cycle to establish RP2D.
Part G: Number of Participants With DLT
An event was considered a DLT if it occurred within the first 21 days of treatment, and met one of following DLT criteria:hematologic toxicity- Grade4 thrombocytopenia persists for >=7 days from the time of AE onset, Grade 4 neutropenia, Grade 4 or Grade 3 febrile neutropenia persists for >=7 days, Grade4 or Grade3 anemia requiring blood transfusion, Grade 3 thrombocytopenia associated with clinically significant bleeding, Grade 3 neutropenia associated with infection as described in CTCAE version 4.0, drug related Grade 3 or 4 non-hematologic toxicity, drug related Grade 3 or 4 nonhematologic laboratory abnormality if any of the following also occur: abnormality leads to hospitalization and abnormality persists for >=7 days from the time of AE onset; drug related toxicity leading to prolonged delay (>2 weeks) in initiating Cycle 2. DLTs were planned to be collected during first cycle to establish RP2D.
Part H: Number of Participants With DLT
An event was considered a DLT if it occurred within the first 21 days of treatment, and met one of following DLT criteria:hematologic toxicity- Grade4 thrombocytopenia persists for >=7 days from the time of AE onset, Grade 4 neutropenia, Grade 4 or Grade 3 febrile neutropenia persists for >=7 days, Grade4 or Grade3 anemia requiring blood transfusion, Grade 3 thrombocytopenia associated with clinically significant bleeding, Grade 3 neutropenia associated with infection as described in CTCAE version 4.0, drug related Grade 3 or 4 non-hematologic toxicity, drug related Grade 3 or 4 nonhematologic laboratory abnormality if any of the following also occur: abnormality leads to hospitalization and abnormality persists for >=7 days from the time of AE onset; drug related toxicity leading to prolonged delay (>2 weeks) in initiating Cycle 2. DLTs were planned to be collected during first cycle to establish RP2D.
Part I: Number of Participants With DLT
An event was considered a DLT if it occurred within the first 21 days of treatment, and met one of following DLT criteria:hematologic toxicity- Grade4 thrombocytopenia persists for >=7 days from the time of AE onset, Grade 4 neutropenia, Grade 4 or Grade 3 febrile neutropenia persists for >=7 days, Grade4 or Grade3 anemia requiring blood transfusion, Grade 3 thrombocytopenia associated with clinically significant bleeding, Grade 3 neutropenia associated with infection as described in CTCAE version 4.0, drug related Grade 3 or 4 non-hematologic toxicity, drug related Grade 3 or 4 nonhematologic laboratory abnormality if any of the following also occur: abnormality leads to hospitalization and abnormality persists for >=7 days from the time of AE onset; drug related toxicity leading to prolonged delay (>2 weeks) in initiating Cycle 2. DLTs were planned to be collected during first cycle to establish RP2D.
Part A: Number of Participants With Non-serious Treatment-emergent Adverse Events (TEAEs), Serious TEAEs (STEAEs) and Adverse Events of Special Interest (AESIs)
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. An SAE is defined as any untoward medical occurrence that, at any dose; results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or any other situation according to medical or scientific judgement. TEAE is any event that was not present prior to the initiation of study treatment or any event already present that worsens in either intensity or frequency following exposure to study treatment. Number of participants with TEAEs, SAEs and AESIs are reported.
Part B: Number of Participants With Non-serious TEAEs, STEAEs and AESIs
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. An SAE is defined as any untoward medical occurrence that, at any dose; results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or any other situation according to medical or scientific judgement. TEAE is any event that was not present prior to the initiation of study treatment or any event already present that worsens in either intensity or frequency following exposure to study treatment. Number of participants with TEAEs, SAEs and AESIs are reported.
Part C: Number of Participants With Non-serious TEAEs, STEAEs and AESIs
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. An SAE is defined as any untoward medical occurrence that, at any dose; results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or any other situation according to medical or scientific judgement. TEAE is any event that was not present prior to the initiation of study treatment or any event already present that worsens in either intensity or frequency following exposure to study treatment. Number of participants with TEAEs, SAEs and AESIs are reported.
Part D: Number of Participants With Non-serious TEAEs, STEAEs and AESIs
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. An SAE is defined as any untoward medical occurrence that, at any dose; results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or any other situation according to medical or scientific judgement. TEAE is any event that was not present prior to the initiation of study treatment or any event already present that worsens in either intensity or frequency following exposure to study treatment. Number of participants with TEAEs, SAEs and AESIs are reported.
Part E: Number of Participants With Non-serious TEAEs, STEAEs and AESIs
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. An SAE is defined as any untoward medical occurrence that, at any dose; results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or any other situation according to medical or scientific judgement. TEAE is any event that was not present prior to the initiation of study treatment or any event already present that worsens in either intensity or frequency following exposure to study treatment. Number of participants with TEAEs, SAEs and AESIs are reported.
Part F: Number of Participants With Non-serious TEAEs, STEAEs and AESIs
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. An SAE is defined as any untoward medical occurrence that, at any dose; results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or any other situation according to medical or scientific judgement. TEAE is any event that was not present prior to the initiation of study treatment or any event already present that worsens in either intensity or frequency following exposure to study treatment. Number of participants with TEAEs, SAEs and AESIs are reported.
Part G: Number of Participants With Non-serious TEAEs, STEAEs and AESIs
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. An SAE is defined as any untoward medical occurrence that, at any dose; results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or any other situation according to medical or scientific judgement. TEAE is any event that was not present prior to the initiation of study treatment or any event already present that worsens in either intensity or frequency following exposure to study treatment.
Part H: Number of Participants With Non-serious TEAEs, STEAEs and AESIs
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. An SAE is defined as any untoward medical occurrence that, at any dose; results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or any other situation according to medical or scientific judgement. TEAE is any event that was not present prior to the initiation of study treatment or any event already present that worsens in either intensity or frequency following exposure to study treatment.
Part I: Number of Participants With Non-serious TEAEs, STEAEs and AESIs
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. An SAE is defined as any untoward medical occurrence that, at any dose; results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or any other situation according to medical or scientific judgement. TEAE is any event that was not present prior to the initiation of study treatment or any event already present that worsens in either intensity or frequency following exposure to study treatment.
Secondary Outcome Measures
Part A: Objective Response Rate
Objective Response Rate is defined as the percentage of participants who achieved confirmed complete response (CR) or partial response (PR), evaluated using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 based on Investigator assessment; where CR=Disappearance of all target lesions. Any pathological lymph nodes must be <10 millimeters (mm) in the short axis. PR=At least a 30 percent (%) decrease in the sum of the diameters of target lesions, taking as a reference, the Baseline sum of the diameters.
Part B: Objective Response Rate
Objective Response Rate is defined as the percentage of participants who achieved confirmed CR or PR, evaluated using RECIST version 1.1 based on Investigator assessment; where CR=Disappearance of all target lesions. Any pathological lymph nodes must be <10 mm in the short axis. PR=At least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the Baseline sum of the diameters.
Part C: Objective Response Rate
Objective Response Rate is defined as the percentage of participants who achieved confirmed CR or PR, evaluated using RECIST version 1.1 based on Investigator assessment; where CR=Disappearance of all target lesions. Any pathological lymph nodes must be <10 mm in the short axis. PR=At least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the Baseline sum of the diameters.
Part D: Objective Response Rate
Objective Response Rate is defined as the percentage of participants who achieved confirmed CR or PR, evaluated using RECIST version 1.1 based on Investigator assessment; where CR=Disappearance of all target lesions. Any pathological lymph nodes must be <10 mm in the short axis. PR=At least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the Baseline sum of the diameters.
Part E: Objective Response Rate
Objective Response Rate is defined as the percentage of participants who achieved confirmed CR or PR, evaluated using RECIST version 1.1 based on Investigator assessment; where CR=Disappearance of all target lesions. Any pathological lymph nodes must be <10 mm in the short axis. PR=At least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the Baseline sum of the diameters.
Part F: Objective Response Rate
Objective Response Rate is defined as the percentage of participants who achieved confirmed CR or PR, evaluated using RECIST version 1.1 based on Investigator assessment; where CR=Disappearance of all target lesions. Any pathological lymph nodes must be <10 mm in the short axis. PR=At least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the Baseline sum of the diameters.
Part G: Objective Response Rate
Objective Response Rate is defined as the percentage of participants who achieved confirmed CR or PR, evaluated using RECIST version 1.1 based on Investigator assessment; where CR=Disappearance of all target lesions. Any pathological lymph nodes must be <10 mm in the short axis. PR=At least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the Baseline sum of the diameters.
Part H: Objective Response Rate
Objective Response Rate is defined as the percentage of participants who achieved confirmed CR or PR, evaluated using RECIST version 1.1 based on Investigator assessment; where CR=Disappearance of all target lesions. Any pathological lymph nodes must be <10 mm in the short axis. PR=At least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the Baseline sum of the diameters.
Part I: Objective Response Rate
Objective Response Rate is defined as the percentage of participants who achieved confirmed CR or PR, evaluated using RECIST version 1.1 based on Investigator assessment; where CR=Disappearance of all target lesions. Any pathological lymph nodes must be <10 mm in the short axis. PR=At least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the Baseline sum of the diameters.
Part A: Duration of Response
Duration of response is defined as the time from first documentation of response (CR or PR) until the time of first documentation of disease progression by RECIST version 1.1 or death by any cause.
Part B: Duration of Response
Duration of response is defined as the time from first documentation of response (CR or PR) until the time of first documentation of disease progression by RECIST version 1.1 or death by any cause. Data is not reported as participants response is still ongoing at the time of primary analysis.
Part C: Duration of Response
Duration of response is defined as the time from first documentation of response (CR or PR) until the time of first documentation of disease progression by RECIST version 1.1 or death by any cause. Data is not reported as participants response is still ongoing at the time of primary analysis.
Part D: Duration of Response
Duration of response is defined as the time from first documentation of response (CR or PR) until the time of first documentation of disease progression by RECIST version 1.1 or death by any cause. Data is not reported as participants response is still ongoing at the time of primary analysis.
Part E: Duration of Response
Duration of response is defined as the time from first documentation of response (CR or PR) until the time of first documentation of disease progression by RECIST version 1.1 or death by any cause.
Part F: Duration of Response
Duration of response is defined as the time from first documentation of response (CR or PR) until the time of first documentation of disease progression by RECIST version 1.1 or death by any cause.
Part G: Duration of Response
Duration of response is defined as the time from first documentation of response (CR or PR) until the time of first documentation of disease progression by RECIST version 1.1 or death by any cause.
Part H: Duration of Response
Duration of response is defined as the time from first documentation of response (CR or PR) until the time of first documentation of disease progression by RECIST version 1.1 or death by any cause.
Part I: Duration of Response
Duration of response is defined as the time from first documentation of response (CR or PR) until the time of first documentation of disease progression by RECIST version 1.1 or death by any cause.
Part A: Disease Control Rate
Disease Control Rate is defined as the percentage of participants who had achieved CR, PR, or stable disease (SD) per RECIST version 1.1.
Part B: Disease Control Rate
Disease Control Rate is defined as the percentage of participants who had achieved CR, PR, or SD per RECIST version 1.1.
Part C: Disease Control Rate
Disease Control Rate is defined as the percentage of participants who had achieved CR, PR, or SD per RECIST version 1.1.
Part D: Disease Control Rate
Disease Control Rate is defined as the percentage of participants who had achieved CR, PR, or SD per RECIST version 1.1.
Part E: Disease Control Rate
Disease Control Rate is defined as the percentage of participants who had achieved CR, PR, or SD per RECIST version 1.1.
Part F: Disease Control Rate
Disease Control Rate is defined as the percentage of participants who had achieved CR, PR, or SD per RECIST version 1.1.
Part G: Disease Control Rate
Disease Control Rate is defined as the percentage of participants who had achieved CR, PR, or SD per RECIST version 1.1.
Part H: Disease Control Rate
Disease Control Rate is defined as the percentage of participants who had achieved CR, PR, or SD per RECIST version 1.1.
Part I: Disease Control Rate
Disease Control Rate is defined as the percentage of participants who had achieved CR, PR, or SD per RECIST version 1.1.
Part A: Progression-free Survival
Progression-free Survival is defined as the date of first dose to the date of disease progression or death due to any cause, whichever occurs earlier. Progressive Disease (PD) is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study.
Part B: Progression-free Survival
Progression-free Survival is defined as the date of first dose to the date of disease progression or death due to any cause, whichever occurs earlier. PD is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study.
Part C: Progression-free Survival
Progression-free Survival is defined as the date of first dose to the date of disease progression or death due to any cause, whichever occurs earlier. PD is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study.
Part D: Progression-free Survival
Progression-free Survival is defined as the date of first dose to the date of disease progression or death due to any cause, whichever occurs earlier. PD is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study.
Part E: Progression-free Survival
Progression-free Survival is defined as the date of first dose to the date of disease progression or death due to any cause, whichever occurs earlier. PD is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study.
Part F: Progression-free Survival
Progression-free Survival is defined as the date of first dose to the date of disease progression or death due to any cause, whichever occurs earlier. PD is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study.
Part G: Progression-free Survival
Progression-free Survival is defined as the date of first dose to the date of disease progression or death due to any cause, whichever occurs earlier.
Part H: Progression-free Survival
Progression-free Survival is defined as the date of first dose to the date of disease progression or death due to any cause, whichever occurs earlier.
Part I: Progression-free Survival
Progression-free Survival is defined as the date of first dose to the date of disease progression or death due to any cause, whichever occurs earlier.
Part A: Number of Participants With Positive Anti-TSR-042 Antibodies
Serum samples were collected at indicated time points and tested for the presence of antibodies that bind to TSR-042. The presence of anti-TSR-042 antibodies were assessed using a tiered approach using electrochemiluminescence (that is, screening, confirmation, titer, and neutralizing antibody assay). Anti-drug Antibody Population consisted of all participants who received at least 1 dose of study treatment and had provided a pre-dose blood sample and at least 1 post-dose blood sample at or after 96 hours.
Part B: Number of Participants With Positive Anti-TSR-042 Antibodies
Serum samples were collected at indicated time points and tested for the presence of antibodies that bind to TSR-042. The presence of anti-TSR-042 antibodies were assessed using a tiered approach using electrochemiluminescence (that is, screening, confirmation, titer, and neutralizing antibody assay).
Part C: Number of Participants With Positive Anti-TSR-042 Antibodies
Serum samples were collected at indicated time points and tested for the presence of antibodies that bind to TSR-042. The presence of anti-TSR-042 antibodies were assessed using a tiered approach using electrochemiluminescence (that is, screening, confirmation, titer, and neutralizing antibody assay).
Part D: Number of Participants With Positive Anti-TSR-042 Antibodies
Serum samples were collected at indicated time points and tested for the presence of antibodies that bind to TSR-042. The presence of anti-TSR-042 antibodies were assessed using a tiered approach using electrochemiluminescence (that is, screening, confirmation, titer, and neutralizing antibody assay).
Part E: Number of Participants With Positive Anti-TSR-042 Antibodies
Serum samples were collected at indicated time points and tested for the presence of antibodies that bind to TSR-042. The presence of anti-TSR-042 antibodies were assessed using a tiered approach using electrochemiluminescence (that is, screening, confirmation, titer, and neutralizing antibody assay).
Part F: Number of Participants With Positive Anti-TSR-042 Antibodies
Serum samples were collected at indicated time points and tested for the presence of antibodies that bind to TSR-042. The presence of anti-TSR-042 antibodies were assessed using a tiered approach using electrochemiluminescence (that is, screening, confirmation, titer, and neutralizing antibody assay).
Part F: Number of Participants With Positive Anti-TSR-022 Antibodies
Serum samples were collected at indicated time points and tested for the presence of antibodies that bind to TSR-022. The presence of anti-TSR-022 antibodies were assessed using a tiered approach using electrochemiluminescence (that is, screening, confirmation, titer, and neutralizing antibody assay).
Part G: Number of Participants With Positive Anti-TSR-042 Antibodies
Serum samples were planned to be collected at indicated time points and tested for the presence of antibodies that bind to TSR-042. The presence of anti-TSR-042 antibodies were planeed to be assessed using a tiered approach using electrochemiluminescence (that is, screening, confirmation, titer, and neutralizing antibody assay).
Part H: Number of Participants With Positive Anti-TSR-042 Antibodies
Serum samples were planned to be collected at indicated time points and tested for the presence of antibodies that bind to TSR-042. The presence of anti-TSR-042 antibodies were planned to be assessed using a tiered approach using electrochemiluminescence (that is, screening, confirmation, titer, and neutralizing antibody assay).
Part H: Number of Participants With Positive Anti-TSR-022 Antibodies
Serum samples were planned to be collected at indicated time points and tested for the presence of antibodies that bind to TSR-022. The presence of anti-TSR-022 antibodies were planned to be assessed using a tiered approach using electrochemiluminescence (that is, screening, confirmation, titer, and neutralizing antibody assay).
Part I: Number of Participants With Positive Anti-TSR-042 Antibodies
Serum samples were planned to be collected at indicated time points and tested for the presence of antibodies that bind to TSR-042. The presence of anti-TSR-042 antibodies were planned to be assessed using a tiered approach using electrochemiluminescence (that is, screening, confirmation, titer, and neutralizing antibody assay).
Part I: Number of Participants With Positive Anti-TSR-022 Antibodies
Serum samples were planned to be collected at indicated time points and tested for the presence of antibodies that bind to TSR-022. The presence of anti-TSR-022 antibodies were planned to be assessed using a tiered approach using electrochemiluminescence (that is, screening, confirmation, titer, and neutralizing antibody assay).
Part A: Area Under the Plasma Concentration From Time Zero to t (AUC[0-t]) of Niraparib
Blood samples were collected at indicated time points. Pharmacokinetic (PK) parameters of niraparib were calculated using non-compartmental methods. PK population consisted of all participants who received at least 1 dose of study treatment and had at least 1 PK sample.
Part A: AUC(0-t) of TSR-042
Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Part B: AUC0-t of TSR-042
Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Part C: AUC0-t of Niraparib
Blood samples were collected at indicated time points. PK parameters of niraparib were calculated using non-compartmental methods.
Part C: AUC0-t of TSR-042
Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Part D: AUC0-t of TSR-042
Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Part E: AUC0-t of TSR-042
Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Part F: AUC0-t of TSR-042
Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Part F: AUC0-t of TSR-022
Blood samples were collected at indicated time points. PK parameters of TSR-022 were calculated using non-compartmental methods.
Part G: AUC0-t of TSR-042
Blood samples were planned to be collected at indicated time points.
Part H: AUC0-t of TSR-042
Blood samples were planned to be collected at indicated time points.
Part H: AUC0-t of TSR-022
Blood samples were planned to be collected at indicated time points.
Part I: AUC0-t of TSR-042
Blood samples were planned to be collected at indicated time points.
Part I: AUC0-t of TSR-022
Blood samples were planned to be collected at indicated time points.
Part A: Area Under the Plasma Concentration From Time Zero to Infinity (AUC[0-infinity]) of Niraparib
Blood samples were collected at indicated time points. PK parameters of niraparib were calculated using non-compartmental methods.
Part A: AUC(0-infinity) of TSR-042
Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Part B: AUC(0-infinity) of TSR-042
Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Part C: AUC(0-infinity) of Niraparib
Blood samples were collected at indicated time points. PK parameters of niraparib were calculated using non-compartmental methods.
Part C: AUC(0-infinity) of TSR-042
Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Part D: AUC(0-infinity) of TSR-042
Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Part E: AUC(0-infinity) of TSR-042
Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Part F: AUC(0-infinity) of TSR-042
Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Part F: AUC(0-infinity) of TSR-022
Blood samples were collected at indicated time points. PK parameters of TSR-022 were calculated using non-compartmental methods.
Part G: AUC(0-infinity) of TSR-042
Blood samples were planned to be collected at indicated time points.
Part H: AUC(0-infinity) of TSR-042
Blood samples were planned to be collected at indicated time points.
Part H: AUC(0-infinity) of TSR-022
Blood samples were planned to be collected at indicated time points.
Part I: AUC(0-infinity) of TSR-042
Blood samples were planned to be collected at indicated time points.
Part I: AUC(0-infinity) of TSR-022
Blood samples were planned to be collected at indicated time points.
Part A: Observed Concentration at the End of the Dosing Interval (Ctau) of Niraparib
Blood samples were collected at indicated time points. PK parameters of niraparib were calculated using non-compartmental methods.
Part A: Ctau of TSR-042
Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Part B: Ctau of TSR-042
Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Part C: Ctau of Niraparib
Blood samples were collected at indicated time points. PK parameters of niraparib were calculated using non-compartmental methods.
Part C: Ctau of TSR-042
Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Part D: Ctau of TSR-042
Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Part E: Ctau of TSR-042
Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Part F: Ctau of TSR-042
Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Part F: Ctau of TSR-022
Blood samples were collected at indicated time points. PK parameters of TSR-022 were calculated using non-compartmental methods.
Part G: Ctau of TSR-042
Blood samples were planned to be collected at indicated time points.
Part H: Ctau of TSR-042
Blood samples were planned to be collected at indicated time points.
Part H: Ctau of TSR-022
Blood samples were planned to be collected at indicated time points.
Part I: Ctau of TSR-042
Blood samples were planned to be collected at indicated time points.
Part I: Ctau of TSR-022
Blood samples were planned to be collected at indicated time points.
Part A: Maximum Observed Plasma (Cmax) of Niraparib
Blood samples were collected at indicated time points. PK parameters of niraparib were calculated using non-compartmental methods.
Part A: Cmax of TSR-042
Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Part B: Cmax of TSR-042
Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Part C: Cmax of Niraparib
Blood samples were collected at indicated time points. PK parameters of niraparib were calculated using non-compartmental methods.
Part C: Cmax of TSR-042
Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Part D: Cmax of TSR-042
Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Part E: Cmax of TSR-042
Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Part F: Cmax of TSR-042
Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Part F: Cmax of TSR-022
Blood samples were collected at indicated time points. PK parameters of TSR-022 were calculated using non-compartmental methods.
Part G: Cmax of TSR-042
Blood samples were planned to be collected at indicated time points.
Part H: Cmax of TSR-042
Blood samples were planned to be collected at indicated time points.
Part H: Cmax of TSR-022
Blood samples were planned to be collected at indicated time points.
Part I: Cmax of TSR-042
Blood samples were planned to be collected at indicated time points.
Part I: Cmax of TSR-022
Blood samples were planned to be collected at indicated time points.
Part A: Clearance After Oral Administration (CL/F) of Niraparib
Blood samples were collected at indicated time points. PK parameters of niraparib were calculated using non-compartmental methods.
Part A: Clearance After Intravenous Administration (CL) of TSR-042
Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Part B: CL of TSR-042
Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Part C: CL/F of Niraparib
Blood samples were collected at indicated time points. PK parameters of niraparib were calculated using non-compartmental methods.
Part C: CL of TSR-042
Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Part D: CL of TSR-042
Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Part E: CL of TSR-042
Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Part F: CL of TSR-042
Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Part F: CL of TSR-022
Blood samples were collected at indicated time points. PK parameters of TSR-022 were calculated using non-compartmental methods.
Part G: CL of TSR-042
Blood samples were planned to be collected at indicated time points.
Part H: CL of TSR-042
Blood samples were planned to be collected at indicated time points.
Part H: CL of TSR-022
Blood samples were planned to be collected at indicated time points.
Part I: CL of TSR-042
Blood samples were planned to be collected at indicated time points.
Part I: CL of TSR-022
Blood samples were planned to be collected at indicated time points.
Part A: Volume of Distribution After Oral Administration (Vz/F) of Niraparib
Blood samples were collected at indicated time points. PK parameters of niraparib were calculated using non-compartmental methods.
Part A: Volume of Distribution After Intravenous Administration (Vz) of of TSR-042
Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Part B: Vz of TSR-042
Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Part C: Vz/F of Niraparib
Blood samples were collected at indicated time points. PK parameters of niraparib were calculated using non-compartmental methods.
Part C: Vz of TSR-042
Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Part D: Vz of TSR-042
Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Part E: Vz of TSR-042
Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Part F: Vz of TSR-042
Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Part F: Vz of TSR-022
Blood samples were collected at indicated time points. PK parameters of TSR-022 were calculated using non-compartmental methods.
Part G: Vz of TSR-042
Blood samples were planned to be collected at indicated time points.
Part H: Vz of TSR-042
Blood samples were planned to be collected at indicated time points.
Part H: Vz of TSR-022
Blood samples were planned to be collected at indicated time points.
Part I: Vz of TSR-042
Blood samples were planned to be collected at indicated time points.
Part I: Vz of TSR-022
Blood samples were planned to be collected at indicated time points.
Part A: AUC at Steady State (AUCss) of Niraparib
Blood samples were collected at indicated time points. PK parameters of niraparib were calculated using non-compartmental methods.
Part A: AUCss of TSR-042
Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Part B: AUCss of TSR-042
Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Part C: AUCss of Niraparib
Blood samples were collected at indicated time points. PK parameters of niraparib were calculated using non-compartmental methods.
Part C: AUCss of TSR-042
Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Part D: AUCss of TSR-042
Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Part E: AUCss of TSR-042
Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Part F: AUCss of TSR-042
Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Part F: AUCss of TSR-022
Blood samples were collected at indicated time points. PK parameters of TSR-022 were calculated using non-compartmental methods.
Part G: AUCss of TSR-042
Blood samples were planned to be collected at indicated time points.
Part H: AUCss of TSR-042
Blood samples were planned to be collected at indicated time points.
Part H: AUCss of TSR-022
Blood samples were planned to be collected at indicated time points.
Part I: AUCss of TSR-042
Blood samples were planned to be collected at indicated time points.
Part I: AUCss of TSR-022
Blood samples were planned to be collected at indicated time points.
Part A: Ctau at Steady State (Ctau,ss) of Niraparib
Blood samples were collected at indicated time points. PK parameters of niraparib were calculated using non-compartmental methods.
Part A: Ctau,ss of TSR-042
Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Part B: Ctau,ss of TSR-042
Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Part C: Ctau,ss of Niraparib
Blood samples were collected at indicated time points. PK parameters of niraparib were calculated using non-compartmental methods.
Part C: Ctau,ss of TSR-042
Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Part D: Ctau,ss of TSR-042
Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Part E: Ctau,ss of TSR-042
Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Part F: Ctau,ss of TSR-042
Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Part F: Ctau,ss of TSR-022
Blood samples were collected at indicated time points. PK parameters of TSR-022 were calculated using non-compartmental methods.
Part G: Ctau,ss of TSR-042
Blood samples were planned to be collected at indicated time points.
Part H: Ctau,ss of TSR-042
Blood samples were planned to be collected at indicated time points.
Part H: Ctau,ss of TSR-022
Blood samples were planned to be collected at indicated time points.
Part I: Ctau,ss of TSR-042
Blood samples were planned to be collected at indicated time points.
Part I: Ctau,ss of TSR-022
Blood samples were planned to be collected at indicated time points.
Part A: Cmax at Steady State (Cmax,ss) of Niraparib
Blood samples were collected at indicated time points. PK parameters of niraparib were calculated using non-compartmental methods.
Part A: Cmax,ss of TSR-042
Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Part B: Cmax,ss of TSR-042
Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Part C: Cmax,ss of Niraparib
Blood samples were collected at indicated time points. PK parameters of niraparib were calculated using non-compartmental methods.
Part C: Cmax,ss of TSR-042
Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Part D: Cmax,ss of TSR-042
Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Part E: Cmax,ss of TSR-042
Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Part F: Cmax,ss of TSR-042
Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Part F: Cmax,ss of TSR-022
Blood samples were collected at indicated time points. PK parameters of TSR-022 were calculated using non-compartmental methods.
Part G: Cmax,ss of TSR-042
Blood samples were planned to be collected at indicated time points.
Part H: Cmax,ss of TSR-042
Blood samples were planned to be collected at indicated time points.
Part H: Cmax,ss of TSR-022
Blood samples were planned to be collected at indicated time points.
Part I: Cmax,ss of TSR-042
Blood samples were planned to be collected at indicated time points.
Part I: Cmax,ss of TSR-022
Blood samples were planned to be collected at indicated time points.
Part A: Time to Reach Maximum Plasma Concentration (Tmax) of Niraparib
Blood samples were collected at indicated time points. PK parameters of niraparib were calculated using non-compartmental methods.
Part A: Tmax of TSR-042
Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Part B: Tmax of TSR-042
Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Part C: Tmax of Niraparib
Blood samples were collected at indicated time points. PK parameters of niraparib were calculated using non-compartmental methods.
Part C: Tmax of TSR-042
Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Part D: Tmax of TSR-042
Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Part E: Tmax of TSR-042
Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Part F: Tmax of TSR-042
Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Part F: Tmax of TSR-022
Blood samples were collected at indicated time points. PK parameters of TSR-022 were calculated using non-compartmental methods.
Part G: Tmax of TSR-042
Blood samples were planned to be collected at indicated time points.
Part H: Tmax of TSR-042
Blood samples were planned to be collected at indicated time points.
Part H: Tmax of TSR-022
Blood samples were planned to be collected at indicated time points.
Part I: Tmax of TSR-042
Blood samples were planned to be collected at indicated time points.
Part I: Tmax of TSR-022
Blood samples were planned to be collected at indicated time points.
Part A: Tmax at Steady State (Tmax,ss) of Niraparib
Blood samples were collected at indicated time points. PK parameters of niraparib were calculated using non-compartmental methods.
Part A: Tmax,ss of TSR-042
Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Part B: Tmax,ss of TSR-042
Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Part C: Tmax,ss of Niraparib
Blood samples were collected at indicated time points. PK parameters of niraparib were calculated using non-compartmental methods.
Part C: Tmax,ss of TSR-042
Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Part D: Tmax,ss of TSR-042
Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Part E: Tmax,ss of TSR-042
Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Part F: Tmax,ss of TSR-042
Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Part F: Tmax,ss of TSR-022
Blood samples were collected at indicated time points. PK parameters of TSR-022 were calculated using non-compartmental methods.
Part G: Tmax,ss of TSR-042
Blood samples were planned to be collected at indicated time points.
Part H: Tmax,ss of TSR-042
Blood samples were planned to be collected at indicated time points.
Part H: Tmax,ss of TSR-022
Blood samples were planned to be collected at indicated time points.
Part I: Tmax,ss of TSR-042
Blood samples were planned to be collected at indicated time points.
Part I: Tmax,ss of TSR-022
Blood samples were planned to be collected at indicated time points.
Part A: Volume of Distribution After Intravenous Administration (Vss) of of TSR-042
Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Part B: Vss of TSR-042
Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Part C: Vss of TSR-042
Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Part D: Vss of TSR-042
Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Part E: Vss of TSR-042
Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Part F: Vss of TSR-042
Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Part F: Vss of TSR-022
Blood samples were collected at indicated time points. PK parameters of TSR-022 were calculated using non-compartmental methods.
Part G: Vss of TSR-042
Blood samples were planned to be collected at indicated time points.
Part H: Vss of TSR-042
Blood samples were planned to be collected at indicated time points.
Part H: Vss of TSR-022
Blood samples were planned to be collected at indicated time points.
Part I: Vss of TSR-042
Blood samples were planned to be collected at indicated time points.
Part I: Vss of TSR-022
Blood samples were planned to be collected at indicated time points.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03307785
Brief Title
Study of Niraparib, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy in Combination With TSR-042
Official Title
Phase 1b Dose-Finding Study of Niraparib, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy in Combination With TSR-042 in Patients With Advanced or Metastatic Cancer
Study Type
Interventional
2. Study Status
Record Verification Date
June 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
October 12, 2017 (Actual)
Primary Completion Date
February 26, 2020 (Actual)
Study Completion Date
April 22, 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Tesaro, Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
Part A: To test the safety and tolerability of combination therapy with Niraparib and TSR-042 and to establish a safe dose that will be used in a Phase 2 study.
Part B: To test the safety and tolerability of combination therapy with Carboplatin-Paclitaxel and TSR-042 and to establish a safe dose that will be used in a Phase 2 study.
Part C: To test the safety and tolerability of combination therapy with Niraparib, TSR-042 and Bevacizumab and to establish a safe dose that will be used in a Phase 2 study.
Part D: To test the safety and tolerability of combination therapy with Carboplatin-Paclitaxel, TSR-042 and Bevacizumab and to establish a safe dose that will be used in a Phase 2 study.
Part E: To test the safety and tolerability of combination therapy with Carboplatin-Pemetrexed and TSR-042 and to establish a safe dose that will be used in a Phase 2 study.
Part F: To test the safety and tolerability of combination therapy with Carboplatin-Pemetrexed, TSR-022 and TSR-042 and to establish a safe dose that will be used in a Phase 2 study.
Part G: To test the safety and tolerability of combination therapy with Carboplatin-nab-Paclitaxel, TSR-042 and to establish a safe dose that will be used in a Phase 2 study.
Part H: To test the safety and tolerability of combination therapy with Carboplatin-nab-Paclitaxel, TSR-022 and TSR-042 and to establish a safe dose that will be used in a Phase 2 study.
Part I: To test the safety and tolerability of combination therapy with Carboplatin-Paclitaxel, TSR-022 and TSR-042 and to establish a safe dose that will be used in a Phase 2 study.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Neoplasms, Metastatic Cancer, Advanced Cancer, Solid Tumor, Non Small Cell Lung Cancer Metastatic, Non Small Cell Lung Cancer Stage IIIB, Non Small Cell Lung Cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
58 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Part A: TSR-042 and niraparib 200 mg QD
Arm Type
Experimental
Arm Description
Patients will receive TSR-042 500 milligram (mg), intravenous (IV) infusion on Day 1 of every cycle (every 3 weeks [Q3W]) for 4 cycles (each cycle is 21 days); followed by TSR-042 1000 mg, IV infusion on Day 1 of every other cycle (every 6 weeks [Q6W]) beginning on Day 1 of Cycle 5 along with niraparib 200 mg, once daily (QD), orally on Days 1 to 21 repeated Q3W.
Arm Title
Part A: TSR-042 and niraparib 300 mg QD
Arm Type
Experimental
Arm Description
Patients will receive TSR-042 500 mg, IV infusion on Day 1 of every cycle (Q3W) for 4 cycles (each cycle is 21 days); followed by TSR-042 1000 mg, IV infusion on Day 1 of every other cycle (Q6W) beginning on Day 1 of Cycle 5 along with niraparib 300 mg, QD, orally on Days 1 to 21 repeated Q3W.
Arm Title
Part B: TSR-042 and carboplatin-paclitaxel
Arm Type
Experimental
Arm Description
Patients will receive TSR-042 500 mg, IV infusion on Day 1 of every cycle (Q3W) for 4 cycles (each cycle is 21 days); followed by TSR-042 1000 mg, IV infusion on Day 1 of every other cycle (Q6W) beginning on Day 1 of Cycle 5 along with carboplatin, IV infusion on Day 1 Q3W and paclitaxel 175 milligram per square meter (mg/m^2), IV infusion on Day 1 Q3W administered for 4 to 6 cycles.
Arm Title
Part C: TSR-042, niraparib 200 mg QD and bevacizumab
Arm Type
Experimental
Arm Description
Patients will receive TSR-042 500 mg, IV infusion on Day 1 of every cycle (Q3W) for 4 cycles (each cycle is 21 days); followed by TSR-042 1000 mg, IV infusion on Day 1 of every other cycle (Q6W) beginning on Day 1 of Cycle 5 along with niraparib 200 mg administered orally on Days 1 to 21 repeated Q3W and bevacizumab 15 mg/kilogram (kg), IV infusion on Day 1 of every 21-day cycle Q3W for up to 15 months.
Arm Title
Part C: TSR-042, niraparib 300 mg QD and bevacizumab
Arm Type
Experimental
Arm Description
Patients will receive TSR-042 500 mg, IV infusion on Day 1 of every cycle (Q3W) for 4 cycles (each cycle is 21 days); followed by TSR-042 1000 mg, IV infusion on Day 1 of every other cycle (Q6W) beginning on Day 1 of Cycle 5 along with niraparib 300 mg administered orally on Days 1 to 21 repeated Q3W and bevacizumab 15 mg/kg, IV infusion on Day 1 of every 21-day cycle Q3W for up to 15 months.
Arm Title
Part D: TSR-042, carboplatin-paclitaxel and bevacizumab
Arm Type
Experimental
Arm Description
Patients will receive TSR-042 500 mg, IV infusion on Day 1 of every cycle (Q3W) for 4 cycles (each cycle is 21 days); followed by TSR-042 1000 mg, IV infusion on Day 1 of every other cycle (Q6W) beginning on Day 1 of Cycle 5 along with carboplatin, IV infusion on Day 1 Q3W and paclitaxel 175 mg/m^2, IV infusion on Day 1 Q3W administered for 4 to 6 cycles; and bevacizumab 15 mg/kg, IV infusion on Day 1 of every 21-day cycle Q3W for up to 15 months.
Arm Title
Part E: TSR-042 and carboplatin-pemetrexed
Arm Type
Experimental
Arm Description
Patients will receive TSR-042 500 mg, IV infusion on Day 1 of every cycle (Q3W) along with carboplatin, IV infusion on Day 1 Q3W and pemetrexed 500 mg/m^2, IV infusion on Day 1 Q3W (with vitamin supplementation) administered for 6 cycles (each cycle is 21 days).
Arm Title
Part F: TSR-042, TSR-022, and carboplatin-pemetrexed
Arm Type
Experimental
Arm Description
Patients will receive TSR-042 500 mg, IV infusion on Day 1 of every cycle (Q3W); and TSR-022 900 mg, IV infusion on Day 1 Q3W along with carboplatin, IV infusion on Day 1 Q3W administered for 5 cycles (each cycle is 21 days); and pemetrexed 500 mg/m^2, IV infusion on Day 1 Q3W (with vitamin supplementation).
Arm Title
Part G: TSR-042 and carboplatin-nab-paclitaxel
Arm Type
Experimental
Arm Description
Patients will receive TSR-042 500 mg, IV infusion on Day 1 of every cycle (Q3W) along with carboplatin, IV infusion on Day 1 Q3W for 4 to 6 cycles (each cycle is 21 days) and nab-paclitaxel 100 mg/m^2, IV infusion on Days 1, 8 and 15 (every week [Q1W]) of every 3 week cycle for 4 to 6 cycles.
Arm Title
Part H: TSR-042, TSR-022, and carboplatin-nab-paclitaxel
Arm Type
Experimental
Arm Description
Patients will receive TSR-042 500 mg, IV infusion on Day 1 of every cycle (Q3W); followed by TSR-022 900 mg, IV infusion on Day 1 Q3W along with carboplatin, IV infusion on Day 1 Q3W for 4 to 6 cycles (each cycle is 21 days) and nab-paclitaxel 100 mg/m^2, IV infusion on Days 1, 8 and 15 (Q1W) of every 3 week cycle for 4 to 6 cycles.
Arm Title
Part I: TSR-042, TSR-022, and carboplatin-paclitaxel
Arm Type
Experimental
Arm Description
Patients will receive TSR-042 500 mg, IV infusion on Day 1 of every cycle (Q3W); followed by TSR-022 900 mg, IV infusion on Day 1 Q3W along with carboplatin, IV infusion on Day 1 Q3W and paclitaxel 175 mg/m^2, IV infusion on Day 1 Q3W for 4 to 6 cycles (each cycle is 21 days).
Intervention Type
Drug
Intervention Name(s)
Niraparib
Other Intervention Name(s)
Zejula
Intervention Description
Niraparib is a potent, orally active PARP1 and PARP2 inhibitor being developed as a treatment for patients with tumors that harbor defects in the homologous recombination DNA repair pathway or that are driven by PARP-mediated transcription factors.
Intervention Type
Drug
Intervention Name(s)
TSR-042
Intervention Description
TSR-042 is a humanized monoclonal antibody that binds with high affinity to PD-1 resulting in inhibition of binding to programmed death receptor ligands 1 and 2 (PD-L1 and PD-L2).
Intervention Type
Drug
Intervention Name(s)
Carboplatin-Paclitaxel
Intervention Description
Carboplatin in combination with paclitaxel is a chemotherapy treatment that has been shown to be efficacious against a variety of different tumor types, including non-small cell lung cancer [NSCLC], ovarian cancer, endometrial cancer, and head and neck cancer.
Intervention Type
Drug
Intervention Name(s)
Bevacizumab
Other Intervention Name(s)
Avastin
Intervention Description
Bevacizumab is a chemotherapy treatment that has been shown to be efficacious against a variety of different cancer types, including colon cancer, lung cancer, glioblastoma, and renal-cell carcinoma. Bevacizumab is in the angiogenesis inhibitor and monoclonal antibody families of medication. It works by slowing the growth of new blood vessels.
Intervention Type
Drug
Intervention Name(s)
TSR-022
Intervention Description
TSR-022 is a monoclonal antibody against TIM-3 (also called HAVCR2), an immune checkpoint receptor. Immune checkpoint proteins are molecules that help to regulate the immune system so it does not mistakenly attack healthy cells. However, they can also keep immune cells from recognizing and killing cancer cells.
TIM-3 is found on the surface of certain T-cells, including tumor-infiltrating T-cells, that have left the bloodstream and migrated into the tumor environment. By binding to and blocking TIM-3, TRS-022 allows for T-cells to become activated so as to enhance T-cell-mediated attacks on tumors. These attacks reduce their growth.
Intervention Type
Drug
Intervention Name(s)
Carboplatin-Pemetrexed
Intervention Description
Pemetrexed and platinum therapy in combination with pembrolizumab (anti-PD-1 antibody) has proven to be efficacious in a first line setting for nonsquamous NSCLC patients
Intervention Type
Drug
Intervention Name(s)
Carboplatin-Nab-Paclitaxel
Intervention Description
Nab-paclitaxel is a formulation of paclitaxel that is indicated for locally advanced or metastatic NSCLC, as first-line treatment in combination with carboplatin in patients who are not candidates for curative surgery or radiation therapy. Nab-paclitaxel has shown increased ORR and time to progression in metastatic breast cancer compared with solvent-based paclitaxel and has shown antitumor activity and improved ORR compared with solvent-based paclitaxel as first-line therapy in patients with NSCLC.
Primary Outcome Measure Information:
Title
Part A: Number of Participants With Dose-limiting Toxicity (DLT)
Description
An event was considered a DLT if it occurred within the first 21 days of treatment, and met one of following DLT criteria:hematologic toxicity- Grade4 thrombocytopenia persists for >=7 days from the time of adverse event(AE) onset, Grade 4 neutropenia, Grade 4 or Grade 3 febrile neutropenia persists for >=7 days, Grade4 or Grade3 anemia requiring blood transfusion, Grade 3 thrombocytopenia associated with clinically significant bleeding, Grade 3 neutropenia associated with infection as described in Common Terminology Criteria for Adverse Events (CTCAE) version 4.0, drug related Grade 3 or 4 non-hematologic toxicity, drug related Grade 3 or 4 nonhematologic laboratory abnormality if any of the following also occur: abnormality leads to hospitalization and abnormality persists for >=7 days from the time of AE onset; drug related toxicity leading to prolonged delay (>2 weeks) in initiating Cycle 2. DLTs were collected during first cycle to establish recommended phase 2 dose (RP2D).
Time Frame
21 days
Title
Part B: Number of Participants With DLT
Description
An event was considered a DLT if it occurred within the first 21 days of treatment, and met one of following DLT criteria:hematologic toxicity- Grade4 thrombocytopenia persists for >=7 days from the time of AE onset, Grade 4 neutropenia, Grade 4 or Grade 3 febrile neutropenia persists for >=7 days, Grade4 or Grade3 anemia requiring blood transfusion, Grade 3 thrombocytopenia associated with clinically significant bleeding, Grade 3 neutropenia associated with infection as described in CTCAE version 4.0, drug related Grade 3 or 4 non-hematologic toxicity, drug related Grade 3 or 4 nonhematologic laboratory abnormality if any of the following also occur: abnormality leads to hospitalization and abnormality persists for >=7 days from the time of AE onset; drug related toxicity leading to prolonged delay (>2 weeks) in initiating Cycle 2. DLTs were collected during first cycle to establish RP2D.
Time Frame
21 days
Title
Part C: Number of Participants With DLT
Description
An event was considered a DLT if it occurred within the first 21 days of treatment, and met one of following DLT criteria:hematologic toxicity- Grade4 thrombocytopenia persists for >=7 days from the time of AE onset, Grade 4 neutropenia, Grade 4 or Grade 3 febrile neutropenia persists for >=7 days, Grade4 or Grade3 anemia requiring blood transfusion, Grade 3 thrombocytopenia associated with clinically significant bleeding, Grade 3 neutropenia associated with infection as described in CTCAE version 4.0, drug related Grade 3 or 4 non-hematologic toxicity, drug related Grade 3 or 4 nonhematologic laboratory abnormality if any of the following also occur: abnormality leads to hospitalization and abnormality persists for >=7 days from the time of AE onset; drug related toxicity leading to prolonged delay (>2 weeks) in initiating Cycle 2. DLTs were collected during first cycle to establish RP2D.
Time Frame
21 days
Title
Part D: Number of Participants With DLT
Description
An event was considered a DLT if it occurred within the first 21 days of treatment, and met one of following DLT criteria:hematologic toxicity- Grade4 thrombocytopenia persists for >=7 days from the time of AE onset, Grade 4 neutropenia, Grade 4 or Grade 3 febrile neutropenia persists for >=7 days, Grade4 or Grade3 anemia requiring blood transfusion, Grade 3 thrombocytopenia associated with clinically significant bleeding, Grade 3 neutropenia associated with infection as described in CTCAE version 4.0, drug related Grade 3 or 4 non-hematologic toxicity, drug related Grade 3 or 4 nonhematologic laboratory abnormality if any of the following also occur: abnormality leads to hospitalization and abnormality persists for >=7 days from the time of AE onset; drug related toxicity leading to prolonged delay (>2 weeks) in initiating Cycle 2. DLTs were collected during first cycle to establish RP2D.
Time Frame
21 days
Title
Part E: Number of Participants With DLT
Description
An event was considered a DLT if it occurred within the first 21 days of treatment, and met one of following DLT criteria:hematologic toxicity- Grade4 thrombocytopenia persists for >=7 days from the time of AE onset, Grade 4 neutropenia, Grade 4 or Grade 3 febrile neutropenia persists for >=7 days, Grade4 or Grade3 anemia requiring blood transfusion, Grade 3 thrombocytopenia associated with clinically significant bleeding, Grade 3 neutropenia associated with infection as described in CTCAE version 4.0, drug related Grade 3 or 4 non-hematologic toxicity, drug related Grade 3 or 4 nonhematologic laboratory abnormality if any of the following also occur: abnormality leads to hospitalization and abnormality persists for >=7 days from the time of AE onset; drug related toxicity leading to prolonged delay (>2 weeks) in initiating Cycle 2. DLTs were collected during first cycle to establish RP2D.
Time Frame
21 days
Title
Part F: Number of Participants With DLT
Description
An event was considered a DLT if it occurred within the first 21 days of treatment, and met one of following DLT criteria:hematologic toxicity- Grade4 thrombocytopenia persists for >=7 days from the time of AE onset, Grade 4 neutropenia, Grade 4 or Grade 3 febrile neutropenia persists for >=7 days, Grade4 or Grade3 anemia requiring blood transfusion, Grade 3 thrombocytopenia associated with clinically significant bleeding, Grade 3 neutropenia associated with infection as described in CTCAE version 4.0, drug related Grade 3 or 4 non-hematologic toxicity, drug related Grade 3 or 4 nonhematologic laboratory abnormality if any of the following also occur: abnormality leads to hospitalization and abnormality persists for >=7 days from the time of AE onset; drug related toxicity leading to prolonged delay (>2 weeks) in initiating Cycle 2. DLTs were collected during first cycle to establish RP2D.
Time Frame
21 days
Title
Part G: Number of Participants With DLT
Description
An event was considered a DLT if it occurred within the first 21 days of treatment, and met one of following DLT criteria:hematologic toxicity- Grade4 thrombocytopenia persists for >=7 days from the time of AE onset, Grade 4 neutropenia, Grade 4 or Grade 3 febrile neutropenia persists for >=7 days, Grade4 or Grade3 anemia requiring blood transfusion, Grade 3 thrombocytopenia associated with clinically significant bleeding, Grade 3 neutropenia associated with infection as described in CTCAE version 4.0, drug related Grade 3 or 4 non-hematologic toxicity, drug related Grade 3 or 4 nonhematologic laboratory abnormality if any of the following also occur: abnormality leads to hospitalization and abnormality persists for >=7 days from the time of AE onset; drug related toxicity leading to prolonged delay (>2 weeks) in initiating Cycle 2. DLTs were planned to be collected during first cycle to establish RP2D.
Time Frame
21 days
Title
Part H: Number of Participants With DLT
Description
An event was considered a DLT if it occurred within the first 21 days of treatment, and met one of following DLT criteria:hematologic toxicity- Grade4 thrombocytopenia persists for >=7 days from the time of AE onset, Grade 4 neutropenia, Grade 4 or Grade 3 febrile neutropenia persists for >=7 days, Grade4 or Grade3 anemia requiring blood transfusion, Grade 3 thrombocytopenia associated with clinically significant bleeding, Grade 3 neutropenia associated with infection as described in CTCAE version 4.0, drug related Grade 3 or 4 non-hematologic toxicity, drug related Grade 3 or 4 nonhematologic laboratory abnormality if any of the following also occur: abnormality leads to hospitalization and abnormality persists for >=7 days from the time of AE onset; drug related toxicity leading to prolonged delay (>2 weeks) in initiating Cycle 2. DLTs were planned to be collected during first cycle to establish RP2D.
Time Frame
21 days
Title
Part I: Number of Participants With DLT
Description
An event was considered a DLT if it occurred within the first 21 days of treatment, and met one of following DLT criteria:hematologic toxicity- Grade4 thrombocytopenia persists for >=7 days from the time of AE onset, Grade 4 neutropenia, Grade 4 or Grade 3 febrile neutropenia persists for >=7 days, Grade4 or Grade3 anemia requiring blood transfusion, Grade 3 thrombocytopenia associated with clinically significant bleeding, Grade 3 neutropenia associated with infection as described in CTCAE version 4.0, drug related Grade 3 or 4 non-hematologic toxicity, drug related Grade 3 or 4 nonhematologic laboratory abnormality if any of the following also occur: abnormality leads to hospitalization and abnormality persists for >=7 days from the time of AE onset; drug related toxicity leading to prolonged delay (>2 weeks) in initiating Cycle 2. DLTs were planned to be collected during first cycle to establish RP2D.
Time Frame
21 days
Title
Part A: Number of Participants With Non-serious Treatment-emergent Adverse Events (TEAEs), Serious TEAEs (STEAEs) and Adverse Events of Special Interest (AESIs)
Description
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. An SAE is defined as any untoward medical occurrence that, at any dose; results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or any other situation according to medical or scientific judgement. TEAE is any event that was not present prior to the initiation of study treatment or any event already present that worsens in either intensity or frequency following exposure to study treatment. Number of participants with TEAEs, SAEs and AESIs are reported.
Time Frame
Up to 28.5 months
Title
Part B: Number of Participants With Non-serious TEAEs, STEAEs and AESIs
Description
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. An SAE is defined as any untoward medical occurrence that, at any dose; results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or any other situation according to medical or scientific judgement. TEAE is any event that was not present prior to the initiation of study treatment or any event already present that worsens in either intensity or frequency following exposure to study treatment. Number of participants with TEAEs, SAEs and AESIs are reported.
Time Frame
Up to 28.5 months
Title
Part C: Number of Participants With Non-serious TEAEs, STEAEs and AESIs
Description
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. An SAE is defined as any untoward medical occurrence that, at any dose; results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or any other situation according to medical or scientific judgement. TEAE is any event that was not present prior to the initiation of study treatment or any event already present that worsens in either intensity or frequency following exposure to study treatment. Number of participants with TEAEs, SAEs and AESIs are reported.
Time Frame
Up to 22.5 months
Title
Part D: Number of Participants With Non-serious TEAEs, STEAEs and AESIs
Description
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. An SAE is defined as any untoward medical occurrence that, at any dose; results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or any other situation according to medical or scientific judgement. TEAE is any event that was not present prior to the initiation of study treatment or any event already present that worsens in either intensity or frequency following exposure to study treatment. Number of participants with TEAEs, SAEs and AESIs are reported.
Time Frame
Up to 9.5 months
Title
Part E: Number of Participants With Non-serious TEAEs, STEAEs and AESIs
Description
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. An SAE is defined as any untoward medical occurrence that, at any dose; results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or any other situation according to medical or scientific judgement. TEAE is any event that was not present prior to the initiation of study treatment or any event already present that worsens in either intensity or frequency following exposure to study treatment. Number of participants with TEAEs, SAEs and AESIs are reported.
Time Frame
Up to 4.4 months
Title
Part F: Number of Participants With Non-serious TEAEs, STEAEs and AESIs
Description
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. An SAE is defined as any untoward medical occurrence that, at any dose; results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or any other situation according to medical or scientific judgement. TEAE is any event that was not present prior to the initiation of study treatment or any event already present that worsens in either intensity or frequency following exposure to study treatment. Number of participants with TEAEs, SAEs and AESIs are reported.
Time Frame
Up to 3.5 months
Title
Part G: Number of Participants With Non-serious TEAEs, STEAEs and AESIs
Description
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. An SAE is defined as any untoward medical occurrence that, at any dose; results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or any other situation according to medical or scientific judgement. TEAE is any event that was not present prior to the initiation of study treatment or any event already present that worsens in either intensity or frequency following exposure to study treatment.
Time Frame
Up to 24 months
Title
Part H: Number of Participants With Non-serious TEAEs, STEAEs and AESIs
Description
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. An SAE is defined as any untoward medical occurrence that, at any dose; results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or any other situation according to medical or scientific judgement. TEAE is any event that was not present prior to the initiation of study treatment or any event already present that worsens in either intensity or frequency following exposure to study treatment.
Time Frame
Up to 24 months
Title
Part I: Number of Participants With Non-serious TEAEs, STEAEs and AESIs
Description
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. An SAE is defined as any untoward medical occurrence that, at any dose; results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or any other situation according to medical or scientific judgement. TEAE is any event that was not present prior to the initiation of study treatment or any event already present that worsens in either intensity or frequency following exposure to study treatment.
Time Frame
Up to 24 months
Secondary Outcome Measure Information:
Title
Part A: Objective Response Rate
Description
Objective Response Rate is defined as the percentage of participants who achieved confirmed complete response (CR) or partial response (PR), evaluated using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 based on Investigator assessment; where CR=Disappearance of all target lesions. Any pathological lymph nodes must be <10 millimeters (mm) in the short axis. PR=At least a 30 percent (%) decrease in the sum of the diameters of target lesions, taking as a reference, the Baseline sum of the diameters.
Time Frame
Up to 28.5 months
Title
Part B: Objective Response Rate
Description
Objective Response Rate is defined as the percentage of participants who achieved confirmed CR or PR, evaluated using RECIST version 1.1 based on Investigator assessment; where CR=Disappearance of all target lesions. Any pathological lymph nodes must be <10 mm in the short axis. PR=At least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the Baseline sum of the diameters.
Time Frame
Up to 28.5 months
Title
Part C: Objective Response Rate
Description
Objective Response Rate is defined as the percentage of participants who achieved confirmed CR or PR, evaluated using RECIST version 1.1 based on Investigator assessment; where CR=Disappearance of all target lesions. Any pathological lymph nodes must be <10 mm in the short axis. PR=At least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the Baseline sum of the diameters.
Time Frame
Up to 22.5 months
Title
Part D: Objective Response Rate
Description
Objective Response Rate is defined as the percentage of participants who achieved confirmed CR or PR, evaluated using RECIST version 1.1 based on Investigator assessment; where CR=Disappearance of all target lesions. Any pathological lymph nodes must be <10 mm in the short axis. PR=At least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the Baseline sum of the diameters.
Time Frame
Up to 9.5 months
Title
Part E: Objective Response Rate
Description
Objective Response Rate is defined as the percentage of participants who achieved confirmed CR or PR, evaluated using RECIST version 1.1 based on Investigator assessment; where CR=Disappearance of all target lesions. Any pathological lymph nodes must be <10 mm in the short axis. PR=At least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the Baseline sum of the diameters.
Time Frame
Up to 4.4 months
Title
Part F: Objective Response Rate
Description
Objective Response Rate is defined as the percentage of participants who achieved confirmed CR or PR, evaluated using RECIST version 1.1 based on Investigator assessment; where CR=Disappearance of all target lesions. Any pathological lymph nodes must be <10 mm in the short axis. PR=At least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the Baseline sum of the diameters.
Time Frame
Up to 3.5 months
Title
Part G: Objective Response Rate
Description
Objective Response Rate is defined as the percentage of participants who achieved confirmed CR or PR, evaluated using RECIST version 1.1 based on Investigator assessment; where CR=Disappearance of all target lesions. Any pathological lymph nodes must be <10 mm in the short axis. PR=At least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the Baseline sum of the diameters.
Time Frame
Up to 24 months
Title
Part H: Objective Response Rate
Description
Objective Response Rate is defined as the percentage of participants who achieved confirmed CR or PR, evaluated using RECIST version 1.1 based on Investigator assessment; where CR=Disappearance of all target lesions. Any pathological lymph nodes must be <10 mm in the short axis. PR=At least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the Baseline sum of the diameters.
Time Frame
Up to 24 months
Title
Part I: Objective Response Rate
Description
Objective Response Rate is defined as the percentage of participants who achieved confirmed CR or PR, evaluated using RECIST version 1.1 based on Investigator assessment; where CR=Disappearance of all target lesions. Any pathological lymph nodes must be <10 mm in the short axis. PR=At least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the Baseline sum of the diameters.
Time Frame
Up to 24 months
Title
Part A: Duration of Response
Description
Duration of response is defined as the time from first documentation of response (CR or PR) until the time of first documentation of disease progression by RECIST version 1.1 or death by any cause.
Time Frame
Up to 28.5 months
Title
Part B: Duration of Response
Description
Duration of response is defined as the time from first documentation of response (CR or PR) until the time of first documentation of disease progression by RECIST version 1.1 or death by any cause. Data is not reported as participants response is still ongoing at the time of primary analysis.
Time Frame
Up to 28.5 months
Title
Part C: Duration of Response
Description
Duration of response is defined as the time from first documentation of response (CR or PR) until the time of first documentation of disease progression by RECIST version 1.1 or death by any cause. Data is not reported as participants response is still ongoing at the time of primary analysis.
Time Frame
Up to 22.5 months
Title
Part D: Duration of Response
Description
Duration of response is defined as the time from first documentation of response (CR or PR) until the time of first documentation of disease progression by RECIST version 1.1 or death by any cause. Data is not reported as participants response is still ongoing at the time of primary analysis.
Time Frame
Up to 9.5 months
Title
Part E: Duration of Response
Description
Duration of response is defined as the time from first documentation of response (CR or PR) until the time of first documentation of disease progression by RECIST version 1.1 or death by any cause.
Time Frame
Up to 4.4 months
Title
Part F: Duration of Response
Description
Duration of response is defined as the time from first documentation of response (CR or PR) until the time of first documentation of disease progression by RECIST version 1.1 or death by any cause.
Time Frame
Up to 3.5 months
Title
Part G: Duration of Response
Description
Duration of response is defined as the time from first documentation of response (CR or PR) until the time of first documentation of disease progression by RECIST version 1.1 or death by any cause.
Time Frame
Up to 24 months
Title
Part H: Duration of Response
Description
Duration of response is defined as the time from first documentation of response (CR or PR) until the time of first documentation of disease progression by RECIST version 1.1 or death by any cause.
Time Frame
Up to 24 months
Title
Part I: Duration of Response
Description
Duration of response is defined as the time from first documentation of response (CR or PR) until the time of first documentation of disease progression by RECIST version 1.1 or death by any cause.
Time Frame
Up to 24 months
Title
Part A: Disease Control Rate
Description
Disease Control Rate is defined as the percentage of participants who had achieved CR, PR, or stable disease (SD) per RECIST version 1.1.
Time Frame
Up to 28.5 months
Title
Part B: Disease Control Rate
Description
Disease Control Rate is defined as the percentage of participants who had achieved CR, PR, or SD per RECIST version 1.1.
Time Frame
Up to 28.5 months
Title
Part C: Disease Control Rate
Description
Disease Control Rate is defined as the percentage of participants who had achieved CR, PR, or SD per RECIST version 1.1.
Time Frame
Up to 22.5 months
Title
Part D: Disease Control Rate
Description
Disease Control Rate is defined as the percentage of participants who had achieved CR, PR, or SD per RECIST version 1.1.
Time Frame
Up to 9.5 months
Title
Part E: Disease Control Rate
Description
Disease Control Rate is defined as the percentage of participants who had achieved CR, PR, or SD per RECIST version 1.1.
Time Frame
Up to 4.4 months
Title
Part F: Disease Control Rate
Description
Disease Control Rate is defined as the percentage of participants who had achieved CR, PR, or SD per RECIST version 1.1.
Time Frame
Up to 3.5 months
Title
Part G: Disease Control Rate
Description
Disease Control Rate is defined as the percentage of participants who had achieved CR, PR, or SD per RECIST version 1.1.
Time Frame
Up to 24 months
Title
Part H: Disease Control Rate
Description
Disease Control Rate is defined as the percentage of participants who had achieved CR, PR, or SD per RECIST version 1.1.
Time Frame
Up to 24 months
Title
Part I: Disease Control Rate
Description
Disease Control Rate is defined as the percentage of participants who had achieved CR, PR, or SD per RECIST version 1.1.
Time Frame
Up to 24 months
Title
Part A: Progression-free Survival
Description
Progression-free Survival is defined as the date of first dose to the date of disease progression or death due to any cause, whichever occurs earlier. Progressive Disease (PD) is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study.
Time Frame
Up to 28.5 months
Title
Part B: Progression-free Survival
Description
Progression-free Survival is defined as the date of first dose to the date of disease progression or death due to any cause, whichever occurs earlier. PD is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study.
Time Frame
Up to 28.5 months
Title
Part C: Progression-free Survival
Description
Progression-free Survival is defined as the date of first dose to the date of disease progression or death due to any cause, whichever occurs earlier. PD is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study.
Time Frame
Up to 22.5 months
Title
Part D: Progression-free Survival
Description
Progression-free Survival is defined as the date of first dose to the date of disease progression or death due to any cause, whichever occurs earlier. PD is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study.
Time Frame
Up to 9.5 months
Title
Part E: Progression-free Survival
Description
Progression-free Survival is defined as the date of first dose to the date of disease progression or death due to any cause, whichever occurs earlier. PD is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study.
Time Frame
Up to 4.4 months
Title
Part F: Progression-free Survival
Description
Progression-free Survival is defined as the date of first dose to the date of disease progression or death due to any cause, whichever occurs earlier. PD is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study.
Time Frame
Up to 3.5 months
Title
Part G: Progression-free Survival
Description
Progression-free Survival is defined as the date of first dose to the date of disease progression or death due to any cause, whichever occurs earlier.
Time Frame
Up to 24 months
Title
Part H: Progression-free Survival
Description
Progression-free Survival is defined as the date of first dose to the date of disease progression or death due to any cause, whichever occurs earlier.
Time Frame
Up to 24 months
Title
Part I: Progression-free Survival
Description
Progression-free Survival is defined as the date of first dose to the date of disease progression or death due to any cause, whichever occurs earlier.
Time Frame
Up to 24 months
Title
Part A: Number of Participants With Positive Anti-TSR-042 Antibodies
Description
Serum samples were collected at indicated time points and tested for the presence of antibodies that bind to TSR-042. The presence of anti-TSR-042 antibodies were assessed using a tiered approach using electrochemiluminescence (that is, screening, confirmation, titer, and neutralizing antibody assay). Anti-drug Antibody Population consisted of all participants who received at least 1 dose of study treatment and had provided a pre-dose blood sample and at least 1 post-dose blood sample at or after 96 hours.
Time Frame
Up to 28.5 months
Title
Part B: Number of Participants With Positive Anti-TSR-042 Antibodies
Description
Serum samples were collected at indicated time points and tested for the presence of antibodies that bind to TSR-042. The presence of anti-TSR-042 antibodies were assessed using a tiered approach using electrochemiluminescence (that is, screening, confirmation, titer, and neutralizing antibody assay).
Time Frame
Up to 28.5 months
Title
Part C: Number of Participants With Positive Anti-TSR-042 Antibodies
Description
Serum samples were collected at indicated time points and tested for the presence of antibodies that bind to TSR-042. The presence of anti-TSR-042 antibodies were assessed using a tiered approach using electrochemiluminescence (that is, screening, confirmation, titer, and neutralizing antibody assay).
Time Frame
Up to 22.5 months
Title
Part D: Number of Participants With Positive Anti-TSR-042 Antibodies
Description
Serum samples were collected at indicated time points and tested for the presence of antibodies that bind to TSR-042. The presence of anti-TSR-042 antibodies were assessed using a tiered approach using electrochemiluminescence (that is, screening, confirmation, titer, and neutralizing antibody assay).
Time Frame
Up to 9.5 months
Title
Part E: Number of Participants With Positive Anti-TSR-042 Antibodies
Description
Serum samples were collected at indicated time points and tested for the presence of antibodies that bind to TSR-042. The presence of anti-TSR-042 antibodies were assessed using a tiered approach using electrochemiluminescence (that is, screening, confirmation, titer, and neutralizing antibody assay).
Time Frame
Up to 4.4 months
Title
Part F: Number of Participants With Positive Anti-TSR-042 Antibodies
Description
Serum samples were collected at indicated time points and tested for the presence of antibodies that bind to TSR-042. The presence of anti-TSR-042 antibodies were assessed using a tiered approach using electrochemiluminescence (that is, screening, confirmation, titer, and neutralizing antibody assay).
Time Frame
Up to 3.5 months
Title
Part F: Number of Participants With Positive Anti-TSR-022 Antibodies
Description
Serum samples were collected at indicated time points and tested for the presence of antibodies that bind to TSR-022. The presence of anti-TSR-022 antibodies were assessed using a tiered approach using electrochemiluminescence (that is, screening, confirmation, titer, and neutralizing antibody assay).
Time Frame
Up to 3.5 months
Title
Part G: Number of Participants With Positive Anti-TSR-042 Antibodies
Description
Serum samples were planned to be collected at indicated time points and tested for the presence of antibodies that bind to TSR-042. The presence of anti-TSR-042 antibodies were planeed to be assessed using a tiered approach using electrochemiluminescence (that is, screening, confirmation, titer, and neutralizing antibody assay).
Time Frame
Up to 24 months
Title
Part H: Number of Participants With Positive Anti-TSR-042 Antibodies
Description
Serum samples were planned to be collected at indicated time points and tested for the presence of antibodies that bind to TSR-042. The presence of anti-TSR-042 antibodies were planned to be assessed using a tiered approach using electrochemiluminescence (that is, screening, confirmation, titer, and neutralizing antibody assay).
Time Frame
Up to 24 months
Title
Part H: Number of Participants With Positive Anti-TSR-022 Antibodies
Description
Serum samples were planned to be collected at indicated time points and tested for the presence of antibodies that bind to TSR-022. The presence of anti-TSR-022 antibodies were planned to be assessed using a tiered approach using electrochemiluminescence (that is, screening, confirmation, titer, and neutralizing antibody assay).
Time Frame
Up to 24 months
Title
Part I: Number of Participants With Positive Anti-TSR-042 Antibodies
Description
Serum samples were planned to be collected at indicated time points and tested for the presence of antibodies that bind to TSR-042. The presence of anti-TSR-042 antibodies were planned to be assessed using a tiered approach using electrochemiluminescence (that is, screening, confirmation, titer, and neutralizing antibody assay).
Time Frame
Up to 24 months
Title
Part I: Number of Participants With Positive Anti-TSR-022 Antibodies
Description
Serum samples were planned to be collected at indicated time points and tested for the presence of antibodies that bind to TSR-022. The presence of anti-TSR-022 antibodies were planned to be assessed using a tiered approach using electrochemiluminescence (that is, screening, confirmation, titer, and neutralizing antibody assay).
Time Frame
Up to 24 months
Title
Part A: Area Under the Plasma Concentration From Time Zero to t (AUC[0-t]) of Niraparib
Description
Blood samples were collected at indicated time points. Pharmacokinetic (PK) parameters of niraparib were calculated using non-compartmental methods. PK population consisted of all participants who received at least 1 dose of study treatment and had at least 1 PK sample.
Time Frame
Cycles 1 and 2: Pre-dose, 1, 2, 4, 6, 8 and 24 hours post-dose (each cycle was 21 days)
Title
Part A: AUC(0-t) of TSR-042
Description
Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Time Frame
Cycles 1 and 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days)
Title
Part B: AUC0-t of TSR-042
Description
Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Time Frame
Cycles 1 and 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days)
Title
Part C: AUC0-t of Niraparib
Description
Blood samples were collected at indicated time points. PK parameters of niraparib were calculated using non-compartmental methods.
Time Frame
Cycles 1 and 2: Pre-dose, 1, 2, 4, 6, 8 and 24 hours post-dose (each cycle was 21 days)
Title
Part C: AUC0-t of TSR-042
Description
Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Time Frame
Cycles 1 and 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days)
Title
Part D: AUC0-t of TSR-042
Description
Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Time Frame
Cycles 1 and 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days)
Title
Part E: AUC0-t of TSR-042
Description
Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Time Frame
Cycle 1: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose; Cycle 2: Pre-dose (each cycle was 21 days)
Title
Part F: AUC0-t of TSR-042
Description
Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Time Frame
Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168 and 336 hours post-dose; Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)
Title
Part F: AUC0-t of TSR-022
Description
Blood samples were collected at indicated time points. PK parameters of TSR-022 were calculated using non-compartmental methods.
Time Frame
Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168 and 336 hours post-dose; Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)
Title
Part G: AUC0-t of TSR-042
Description
Blood samples were planned to be collected at indicated time points.
Time Frame
Cycles 1 and 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose; Cycle 2: Pre-dose (each cycle was 21 days)
Title
Part H: AUC0-t of TSR-042
Description
Blood samples were planned to be collected at indicated time points.
Time Frame
Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168 and 336 hours post-dose; Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)
Title
Part H: AUC0-t of TSR-022
Description
Blood samples were planned to be collected at indicated time points.
Time Frame
Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168 and 336 hours post-dose; Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)
Title
Part I: AUC0-t of TSR-042
Description
Blood samples were planned to be collected at indicated time points.
Time Frame
Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168 and 336 hours post-dose; Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)
Title
Part I: AUC0-t of TSR-022
Description
Blood samples were planned to be collected at indicated time points.
Time Frame
Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168 and 336 hours post-dose; Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)
Title
Part A: Area Under the Plasma Concentration From Time Zero to Infinity (AUC[0-infinity]) of Niraparib
Description
Blood samples were collected at indicated time points. PK parameters of niraparib were calculated using non-compartmental methods.
Time Frame
Cycles 1 and 2: Pre-dose, 1, 2, 4, 6, 8 and 24 hours post-dose (each cycle was 21 days)
Title
Part A: AUC(0-infinity) of TSR-042
Description
Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Time Frame
Cycles 1 and 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days)
Title
Part B: AUC(0-infinity) of TSR-042
Description
Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Time Frame
Cycles 1 and 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days)
Title
Part C: AUC(0-infinity) of Niraparib
Description
Blood samples were collected at indicated time points. PK parameters of niraparib were calculated using non-compartmental methods.
Time Frame
Cycles 1 and 2: Pre-dose, 1, 2, 4, 6, 8 and 24 hours post-dose (each cycle was 21 days)
Title
Part C: AUC(0-infinity) of TSR-042
Description
Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Time Frame
Cycles 1 and 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days)
Title
Part D: AUC(0-infinity) of TSR-042
Description
Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Time Frame
Cycles 1 and 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days)
Title
Part E: AUC(0-infinity) of TSR-042
Description
Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Time Frame
Cycle 1: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose; Cycle 2: Pre-dose (each cycle was 21 days)
Title
Part F: AUC(0-infinity) of TSR-042
Description
Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Time Frame
Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168, and 336 hours post-dose; Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)
Title
Part F: AUC(0-infinity) of TSR-022
Description
Blood samples were collected at indicated time points. PK parameters of TSR-022 were calculated using non-compartmental methods.
Time Frame
Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168 and 336 hours post-dose; Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168 and 336 hours post-dose (each cycle was 21 days)
Title
Part G: AUC(0-infinity) of TSR-042
Description
Blood samples were planned to be collected at indicated time points.
Time Frame
Cycles 1 and 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose; Cycle 2: Pre-dose (each cycle was 21 days)
Title
Part H: AUC(0-infinity) of TSR-042
Description
Blood samples were planned to be collected at indicated time points.
Time Frame
Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168 and 336 hours post-dose; Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 96, 168, and 336 hours post-dose (each cycle was 21 days)
Title
Part H: AUC(0-infinity) of TSR-022
Description
Blood samples were planned to be collected at indicated time points.
Time Frame
Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168 and 336 hours post-dose; Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 96, 168, and 336 hours post-dose (each cycle was 21 days)
Title
Part I: AUC(0-infinity) of TSR-042
Description
Blood samples were planned to be collected at indicated time points.
Time Frame
Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168 and 336 hours post-dose; Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)
Title
Part I: AUC(0-infinity) of TSR-022
Description
Blood samples were planned to be collected at indicated time points.
Time Frame
Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168 and 336 hours post-dose; Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)
Title
Part A: Observed Concentration at the End of the Dosing Interval (Ctau) of Niraparib
Description
Blood samples were collected at indicated time points. PK parameters of niraparib were calculated using non-compartmental methods.
Time Frame
Cycle 1: Pre-dose, 1, 2, 4, 6, 8 and 24 hours post-dose (each cycle was 21 days)
Title
Part A: Ctau of TSR-042
Description
Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Time Frame
Cycle 1: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose (each cycle was 21 days)
Title
Part B: Ctau of TSR-042
Description
Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Time Frame
Cycle 1: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose (each cycle was 21 days)
Title
Part C: Ctau of Niraparib
Description
Blood samples were collected at indicated time points. PK parameters of niraparib were calculated using non-compartmental methods.
Time Frame
Cycle 1: Pre-dose, 1, 2, 4, 6, 8 and 24 hours post-dose (each cycle was 21 days)
Title
Part C: Ctau of TSR-042
Description
Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Time Frame
Cycle 1: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose (each cycle was 21 days)
Title
Part D: Ctau of TSR-042
Description
Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Time Frame
Cycle 1: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose (each cycle was 21 days)
Title
Part E: Ctau of TSR-042
Description
Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Time Frame
Cycle 1: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)
Title
Part F: Ctau of TSR-042
Description
Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Time Frame
Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)
Title
Part F: Ctau of TSR-022
Description
Blood samples were collected at indicated time points. PK parameters of TSR-022 were calculated using non-compartmental methods.
Time Frame
Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)
Title
Part G: Ctau of TSR-042
Description
Blood samples were planned to be collected at indicated time points.
Time Frame
Cycle 1: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)
Title
Part H: Ctau of TSR-042
Description
Blood samples were planned to be collected at indicated time points.
Time Frame
Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168 and 336 hours post-dose (each cycle was 21 days)
Title
Part H: Ctau of TSR-022
Description
Blood samples were planned to be collected at indicated time points.
Time Frame
Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168 and 336 hours post-dose (each cycle was 21 days)
Title
Part I: Ctau of TSR-042
Description
Blood samples were planned to be collected at indicated time points.
Time Frame
Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168 and 336 hours post-dose (each cycle was 21 days)
Title
Part I: Ctau of TSR-022
Description
Blood samples were planned to be collected at indicated time points.
Time Frame
Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168 and 336 hours post-dose (each cycle was 21 days)
Title
Part A: Maximum Observed Plasma (Cmax) of Niraparib
Description
Blood samples were collected at indicated time points. PK parameters of niraparib were calculated using non-compartmental methods.
Time Frame
Cycle 1: Pre-dose, 1, 2, 4, 6, 8 and 24 hours post-dose (each cycle was 21 days)
Title
Part A: Cmax of TSR-042
Description
Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Time Frame
Cycle 1: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose (each cycle was 21 days)
Title
Part B: Cmax of TSR-042
Description
Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Time Frame
Cycle 1: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose (each cycle was 21 days)
Title
Part C: Cmax of Niraparib
Description
Blood samples were collected at indicated time points. PK parameters of niraparib were calculated using non-compartmental methods.
Time Frame
Cycle 1: Pre-dose, 1, 2, 4, 6, 8 and 24 hours post-dose (each cycle was 21 days)
Title
Part C: Cmax of TSR-042
Description
Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Time Frame
Cycle 1: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose (each cycle was 21 days)
Title
Part D: Cmax of TSR-042
Description
Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Time Frame
Cycle 1: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose (each cycle was 21 days)
Title
Part E: Cmax of TSR-042
Description
Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Time Frame
Cycle 1: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)
Title
Part F: Cmax of TSR-042
Description
Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Time Frame
Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)
Title
Part F: Cmax of TSR-022
Description
Blood samples were collected at indicated time points. PK parameters of TSR-022 were calculated using non-compartmental methods.
Time Frame
Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168 and 336 hours post-dose (each cycle was 21 days)
Title
Part G: Cmax of TSR-042
Description
Blood samples were planned to be collected at indicated time points.
Time Frame
Cycle 1: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)
Title
Part H: Cmax of TSR-042
Description
Blood samples were planned to be collected at indicated time points.
Time Frame
Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168 and 336 hours post-dose (each cycle was 21 days)
Title
Part H: Cmax of TSR-022
Description
Blood samples were planned to be collected at indicated time points.
Time Frame
Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168 and 336 hours post-dose (each cycle was 21 days)
Title
Part I: Cmax of TSR-042
Description
Blood samples were planned to be collected at indicated time points.
Time Frame
Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168 and 336 hours post-dose (each cycle was 21 days)
Title
Part I: Cmax of TSR-022
Description
Blood samples were planned to be collected at indicated time points.
Time Frame
Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168 and 336 hours post-dose (each cycle was 21 days)
Title
Part A: Clearance After Oral Administration (CL/F) of Niraparib
Description
Blood samples were collected at indicated time points. PK parameters of niraparib were calculated using non-compartmental methods.
Time Frame
Cycles 1 and 2: Pre-dose, 1, 2, 4, 6, 8 and 24 hours post-dose (each cycle was 21 days)
Title
Part A: Clearance After Intravenous Administration (CL) of TSR-042
Description
Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Time Frame
Cycles 1 and 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days)
Title
Part B: CL of TSR-042
Description
Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Time Frame
Cycles 1 and 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days)
Title
Part C: CL/F of Niraparib
Description
Blood samples were collected at indicated time points. PK parameters of niraparib were calculated using non-compartmental methods.
Time Frame
Cycles 1 and 2: Pre-dose, 1, 2, 4, 6, 8 and 24 hours post-dose (each cycle was 21 days)
Title
Part C: CL of TSR-042
Description
Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Time Frame
Cycles 1 and 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days)
Title
Part D: CL of TSR-042
Description
Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Time Frame
Cycles 1 and 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days)
Title
Part E: CL of TSR-042
Description
Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Time Frame
Cycle 1: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose; Cycle 2: Pre-dose (each cycle was 21 days)
Title
Part F: CL of TSR-042
Description
Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Time Frame
Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168, and 336 hours post-dose; Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)
Title
Part F: CL of TSR-022
Description
Blood samples were collected at indicated time points. PK parameters of TSR-022 were calculated using non-compartmental methods.
Time Frame
Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168, and 336 hours post-dose; Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)
Title
Part G: CL of TSR-042
Description
Blood samples were planned to be collected at indicated time points.
Time Frame
Cycles 1 and 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose; Cycle 2: Pre-dose (each cycle was 21 days)
Title
Part H: CL of TSR-042
Description
Blood samples were planned to be collected at indicated time points.
Time Frame
Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168 and 336 hours post-dose; Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 96, 168, and 336 hours post-dose (each cycle was 21 days)
Title
Part H: CL of TSR-022
Description
Blood samples were planned to be collected at indicated time points.
Time Frame
Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168 and 336 hours post-dose; Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 96, 168, and 336 hours post-dose (each cycle was 21 days)
Title
Part I: CL of TSR-042
Description
Blood samples were planned to be collected at indicated time points.
Time Frame
Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168 and 336 hours post-dose; Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)
Title
Part I: CL of TSR-022
Description
Blood samples were planned to be collected at indicated time points.
Time Frame
Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168 and 336 hours post-dose; Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)
Title
Part A: Volume of Distribution After Oral Administration (Vz/F) of Niraparib
Description
Blood samples were collected at indicated time points. PK parameters of niraparib were calculated using non-compartmental methods.
Time Frame
Cycles 1 and 2: Pre-dose, 1, 2, 4, 6, 8 and 24 hours post-dose (each cycle was 21 days)
Title
Part A: Volume of Distribution After Intravenous Administration (Vz) of of TSR-042
Description
Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Time Frame
Cycles 1 and 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days)
Title
Part B: Vz of TSR-042
Description
Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Time Frame
Cycles 1 and 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days)
Title
Part C: Vz/F of Niraparib
Description
Blood samples were collected at indicated time points. PK parameters of niraparib were calculated using non-compartmental methods.
Time Frame
Cycles 1 and 2: Pre-dose, 1, 2, 4, 6, 8 and 24 hours post-dose (each cycle was 21 days)
Title
Part C: Vz of TSR-042
Description
Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Time Frame
Cycles 1 and 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days)
Title
Part D: Vz of TSR-042
Description
Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Time Frame
Cycles 1 and 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days)
Title
Part E: Vz of TSR-042
Description
Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Time Frame
Cycle 1: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose; Cycle 2: Pre-dose (each cycle was 21 days)
Title
Part F: Vz of TSR-042
Description
Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Time Frame
Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168, and 336 hours post-dose; Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)
Title
Part F: Vz of TSR-022
Description
Blood samples were collected at indicated time points. PK parameters of TSR-022 were calculated using non-compartmental methods.
Time Frame
Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168, and 336 hours post-dose; Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)
Title
Part G: Vz of TSR-042
Description
Blood samples were planned to be collected at indicated time points.
Time Frame
Cycles 1 and 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose; Cycle 2: Pre-dose (each cycle was 21 days)
Title
Part H: Vz of TSR-042
Description
Blood samples were planned to be collected at indicated time points.
Time Frame
Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168 and 336 hours post-dose; Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 96, 168, and 336 hours post-dose (each cycle was 21 days)
Title
Part H: Vz of TSR-022
Description
Blood samples were planned to be collected at indicated time points.
Time Frame
Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168 and 336 hours post-dose; Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 96, 168, and 336 hours post-dose (each cycle was 21 days)
Title
Part I: Vz of TSR-042
Description
Blood samples were planned to be collected at indicated time points.
Time Frame
Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168 and 336 hours post-dose; Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)
Title
Part I: Vz of TSR-022
Description
Blood samples were planned to be collected at indicated time points.
Time Frame
Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168 and 336 hours post-dose; Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)
Title
Part A: AUC at Steady State (AUCss) of Niraparib
Description
Blood samples were collected at indicated time points. PK parameters of niraparib were calculated using non-compartmental methods.
Time Frame
Cycle 2: Pre-dose, 1, 2, 4, 6, 8 and 24 hours post-dose (each cycle was 21 days)
Title
Part A: AUCss of TSR-042
Description
Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Time Frame
Cycle 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days)
Title
Part B: AUCss of TSR-042
Description
Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Time Frame
Cycle 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days)
Title
Part C: AUCss of Niraparib
Description
Blood samples were collected at indicated time points. PK parameters of niraparib were calculated using non-compartmental methods.
Time Frame
Cycle 2: Pre-dose, 1, 2, 4, 6, 8 and 24 hours post-dose (each cycle was 21 days)
Title
Part C: AUCss of TSR-042
Description
Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Time Frame
Cycle 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days)
Title
Part D: AUCss of TSR-042
Description
Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Time Frame
Cycle 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days)
Title
Part E: AUCss of TSR-042
Description
Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Time Frame
Cycle 2: Pre-dose (each cycle was 21 days)
Title
Part F: AUCss of TSR-042
Description
Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Time Frame
Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)
Title
Part F: AUCss of TSR-022
Description
Blood samples were collected at indicated time points. PK parameters of TSR-022 were calculated using non-compartmental methods.
Time Frame
Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)
Title
Part G: AUCss of TSR-042
Description
Blood samples were planned to be collected at indicated time points.
Time Frame
Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)
Title
Part H: AUCss of TSR-042
Description
Blood samples were planned to be collected at indicated time points.
Time Frame
Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 96, 168, and 336 hours post-dose (each cycle was 21 days)
Title
Part H: AUCss of TSR-022
Description
Blood samples were planned to be collected at indicated time points.
Time Frame
Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 96, 168, and 336 hours post-dose (each cycle was 21 days)
Title
Part I: AUCss of TSR-042
Description
Blood samples were planned to be collected at indicated time points.
Time Frame
Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)
Title
Part I: AUCss of TSR-022
Description
Blood samples were planned to be collected at indicated time points.
Time Frame
Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)
Title
Part A: Ctau at Steady State (Ctau,ss) of Niraparib
Description
Blood samples were collected at indicated time points. PK parameters of niraparib were calculated using non-compartmental methods.
Time Frame
Cycle 2: Pre-dose, 1, 2, 4, 6, 8 and 24 hours post-dose; Cycles 5 and 11: Pre-dose, 2 hours post-dose (each cycle was 21 days)
Title
Part A: Ctau,ss of TSR-042
Description
Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Time Frame
Cycle 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days)
Title
Part B: Ctau,ss of TSR-042
Description
Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Time Frame
Cycle 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days)
Title
Part C: Ctau,ss of Niraparib
Description
Blood samples were collected at indicated time points. PK parameters of niraparib were calculated using non-compartmental methods.
Time Frame
Cycle 2: Pre-dose, 1, 2, 4, 6, 8 and 24 hours post-dose; Cycles 5 and 11: Pre-dose, 2 hours post-dose (each cycle was 21 days)
Title
Part C: Ctau,ss of TSR-042
Description
Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Time Frame
Cycle 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days)
Title
Part D: Ctau,ss of TSR-042
Description
Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Time Frame
Cycle 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days)
Title
Part E: Ctau,ss of TSR-042
Description
Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Time Frame
Cycle 2: Pre-dose (each cycle was 21 days)
Title
Part F: Ctau,ss of TSR-042
Description
Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Time Frame
Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)
Title
Part F: Ctau,ss of TSR-022
Description
Blood samples were collected at indicated time points. PK parameters of TSR-022 were calculated using non-compartmental methods.
Time Frame
Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)
Title
Part G: Ctau,ss of TSR-042
Description
Blood samples were planned to be collected at indicated time points.
Time Frame
Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)
Title
Part H: Ctau,ss of TSR-042
Description
Blood samples were planned to be collected at indicated time points.
Time Frame
Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 96, 168, and 336 hours post-dose (each cycle was 21 days)
Title
Part H: Ctau,ss of TSR-022
Description
Blood samples were planned to be collected at indicated time points.
Time Frame
Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 96, 168, and 336 hours post-dose (each cycle was 21 days)
Title
Part I: Ctau,ss of TSR-042
Description
Blood samples were planned to be collected at indicated time points.
Time Frame
Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)
Title
Part I: Ctau,ss of TSR-022
Description
Blood samples were planned to be collected at indicated time points.
Time Frame
Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)
Title
Part A: Cmax at Steady State (Cmax,ss) of Niraparib
Description
Blood samples were collected at indicated time points. PK parameters of niraparib were calculated using non-compartmental methods.
Time Frame
Cycle 2: Pre-dose, 1, 2, 4, 6, 8 and 24 hours post-dose; Cycles 5 and 11: Pre-dose, 2 hours post-dose (each cycle was 21 days)
Title
Part A: Cmax,ss of TSR-042
Description
Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Time Frame
Cycle 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days)
Title
Part B: Cmax,ss of TSR-042
Description
Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Time Frame
Cycle 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days)
Title
Part C: Cmax,ss of Niraparib
Description
Blood samples were collected at indicated time points. PK parameters of niraparib were calculated using non-compartmental methods.
Time Frame
Cycle 2: Pre-dose, 1, 2, 4, 6, 8 and 24 hours post-dose; Cycles 5 and 11: Pre-dose, 2 hours post-dose (each cycle was 21 days)
Title
Part C: Cmax,ss of TSR-042
Description
Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Time Frame
Cycle 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days)
Title
Part D: Cmax,ss of TSR-042
Description
Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Time Frame
Cycle 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days)
Title
Part E: Cmax,ss of TSR-042
Description
Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Time Frame
Cycle 2: Pre-dose (each cycle was 21 days)
Title
Part F: Cmax,ss of TSR-042
Description
Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Time Frame
Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)
Title
Part F: Cmax,ss of TSR-022
Description
Blood samples were collected at indicated time points. PK parameters of TSR-022 were calculated using non-compartmental methods.
Time Frame
Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)
Title
Part G: Cmax,ss of TSR-042
Description
Blood samples were planned to be collected at indicated time points.
Time Frame
Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)
Title
Part H: Cmax,ss of TSR-042
Description
Blood samples were planned to be collected at indicated time points.
Time Frame
Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 96, 168, and 336 hours post-dose (each cycle was 21 days)
Title
Part H: Cmax,ss of TSR-022
Description
Blood samples were planned to be collected at indicated time points.
Time Frame
Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 96, 168, and 336 hours post-dose (each cycle was 21 days)
Title
Part I: Cmax,ss of TSR-042
Description
Blood samples were planned to be collected at indicated time points.
Time Frame
Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)
Title
Part I: Cmax,ss of TSR-022
Description
Blood samples were planned to be collected at indicated time points.
Time Frame
Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)
Title
Part A: Time to Reach Maximum Plasma Concentration (Tmax) of Niraparib
Description
Blood samples were collected at indicated time points. PK parameters of niraparib were calculated using non-compartmental methods.
Time Frame
Cycle 1: Pre-dose, 1, 2, 4, 6, 8 and 24 hours post-dose (each cycle was 21 days)
Title
Part A: Tmax of TSR-042
Description
Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Time Frame
Cycle 1: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose (each cycle was 21 days)
Title
Part B: Tmax of TSR-042
Description
Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Time Frame
Cycle 1: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose (each cycle was 21 days)
Title
Part C: Tmax of Niraparib
Description
Blood samples were collected at indicated time points. PK parameters of niraparib were calculated using non-compartmental methods.
Time Frame
Cycle 1: Pre-dose, 1, 2, 4, 6, 8 and 24 hours post-dose (each cycle was 21 days)
Title
Part C: Tmax of TSR-042
Description
Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Time Frame
Cycle 1: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose (each cycle was 21 days)
Title
Part D: Tmax of TSR-042
Description
Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Time Frame
Cycle 1: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose (each cycle was 21 days)
Title
Part E: Tmax of TSR-042
Description
Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Time Frame
Cycle 1: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)
Title
Part F: Tmax of TSR-042
Description
Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Time Frame
Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)
Title
Part F: Tmax of TSR-022
Description
Blood samples were collected at indicated time points. PK parameters of TSR-022 were calculated using non-compartmental methods.
Time Frame
Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)
Title
Part G: Tmax of TSR-042
Description
Blood samples were planned to be collected at indicated time points.
Time Frame
Cycle 1: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)
Title
Part H: Tmax of TSR-042
Description
Blood samples were planned to be collected at indicated time points.
Time Frame
Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168 and 336 hours post-dose (each cycle was 21 days)
Title
Part H: Tmax of TSR-022
Description
Blood samples were planned to be collected at indicated time points.
Time Frame
Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168 and 336 hours post-dose (each cycle was 21 days)
Title
Part I: Tmax of TSR-042
Description
Blood samples were planned to be collected at indicated time points.
Time Frame
Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168 and 336 hours post-dose (each cycle was 21 days)
Title
Part I: Tmax of TSR-022
Description
Blood samples were planned to be collected at indicated time points.
Time Frame
Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168 and 336 hours post-dose (each cycle was 21 days)
Title
Part A: Tmax at Steady State (Tmax,ss) of Niraparib
Description
Blood samples were collected at indicated time points. PK parameters of niraparib were calculated using non-compartmental methods.
Time Frame
Cycle 2: Pre-dose, 1, 2, 4, 6, 8 and 24 hours post-dose; Cycles 5 and 11: Pre-dose, 2 hours post-dose (each cycle was 21 days)
Title
Part A: Tmax,ss of TSR-042
Description
Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Time Frame
Cycle 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days)
Title
Part B: Tmax,ss of TSR-042
Description
Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Time Frame
Cycle 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days)
Title
Part C: Tmax,ss of Niraparib
Description
Blood samples were collected at indicated time points. PK parameters of niraparib were calculated using non-compartmental methods.
Time Frame
Cycle 2: Pre-dose, 1, 2, 4, 6, 8 and 24 hours post-dose; Cycles 5 and 11: Pre-dose, 2 hours post-dose (each cycle was 21 days)
Title
Part C: Tmax,ss of TSR-042
Description
Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Time Frame
Cycle 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days)
Title
Part D: Tmax,ss of TSR-042
Description
Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Time Frame
Cycle 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days)
Title
Part E: Tmax,ss of TSR-042
Description
Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Time Frame
Cycle 2: Pre-dose (each cycle was 21 days)
Title
Part F: Tmax,ss of TSR-042
Description
Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Time Frame
Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)
Title
Part F: Tmax,ss of TSR-022
Description
Blood samples were collected at indicated time points. PK parameters of TSR-022 were calculated using non-compartmental methods.
Time Frame
Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)
Title
Part G: Tmax,ss of TSR-042
Description
Blood samples were planned to be collected at indicated time points.
Time Frame
Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)
Title
Part H: Tmax,ss of TSR-042
Description
Blood samples were planned to be collected at indicated time points.
Time Frame
Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 96, 168, and 336 hours post-dose (each cycle was 21 days)
Title
Part H: Tmax,ss of TSR-022
Description
Blood samples were planned to be collected at indicated time points.
Time Frame
Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 96, 168, and 336 hours post-dose (each cycle was 21 days)
Title
Part I: Tmax,ss of TSR-042
Description
Blood samples were planned to be collected at indicated time points.
Time Frame
Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)
Title
Part I: Tmax,ss of TSR-022
Description
Blood samples were planned to be collected at indicated time points.
Time Frame
Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)
Title
Part A: Volume of Distribution After Intravenous Administration (Vss) of of TSR-042
Description
Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Time Frame
Cycle 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days)
Title
Part B: Vss of TSR-042
Description
Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Time Frame
Cycle 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days)
Title
Part C: Vss of TSR-042
Description
Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Time Frame
Cycle 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days)
Title
Part D: Vss of TSR-042
Description
Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Time Frame
Cycle 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days)
Title
Part E: Vss of TSR-042
Description
Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Time Frame
Cycle 2: Pre-dose (each cycle was 21 days)
Title
Part F: Vss of TSR-042
Description
Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods.
Time Frame
Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)
Title
Part F: Vss of TSR-022
Description
Blood samples were collected at indicated time points. PK parameters of TSR-022 were calculated using non-compartmental methods.
Time Frame
Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)
Title
Part G: Vss of TSR-042
Description
Blood samples were planned to be collected at indicated time points.
Time Frame
Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)
Title
Part H: Vss of TSR-042
Description
Blood samples were planned to be collected at indicated time points.
Time Frame
Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 96, 168, and 336 hours post-dose (each cycle was 21 days)
Title
Part H: Vss of TSR-022
Description
Blood samples were planned to be collected at indicated time points.
Time Frame
Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 96, 168, and 336 hours post-dose (each cycle was 21 days)
Title
Part I: Vss of TSR-042
Description
Blood samples were planned to be collected at indicated time points.
Time Frame
Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)
Title
Part I: Vss of TSR-022
Description
Blood samples were planned to be collected at indicated time points.
Time Frame
Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Patient has histologically or cytologically proven advanced (unresectable) or metastatic cancer as outlined below according to study part and disease type:
Part A: Patients with previously treated advanced or metastatic cancer. Patient may have received no more than 4 lines of treatment for advanced or metastatic cancer. Hormonal treatment will not be considered a prior line of treatment.
Part B: Patients with advanced or metastatic cancer for which treatment with carboplatin-paclitaxel is considered appropriate therapy. Patient may have received no more than 1 prior line of chemotherapy in the metastatic setting. Hormonal treatment will not be considered a prior line of treatment.
Part C: Patients with previously treated advanced or metastatic cancer. Patient may have received no more than 4 lines of treatment for advanced or metastatic cancer. Hormonal treatment will not be considered a prior line of treatment.
Part D: Patients in whom carboplatin-paclitaxel and bevacizumab is considered appropriate therapy. Patient may have received no more than 1 prior line of chemotherapy in the metastatic setting. Hormonal treatment will not be considered a prior line of treatment.
Part E and F: Patients who have not received prior systemic therapy, including targeted therapy and biologic agents, for their advanced or metastatic (Stage ≥ IIIB or IV) Non-Squamous NSCLC. Patients who have received neoadjuvant or adjuvant therapy are eligible as long as development of advanced or metastatic disease occurred at least 12 months after completion of neoadjuvant or adjuvant therapy.
Part G, H, and I: Patients who have not received prior systemic therapy, including targeted therapy and biologic agents, for their advanced or metastatic (Stage ≥ IIIB or IV) NSCLC. Patients who have received neoadjuvant or adjuvant therapy are eligible as long as development of advanced or metastatic disease occurred at least 12 months after completion of neoadjuvant or adjuvant therapy.
Patient has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
Patient has adequate organ function.
Female patient has a negative serum pregnancy test within 72 hours prior to taking study treatment if of childbearing potential and agrees to abstain from activities that could result in pregnancy from screening through 180 days after the last dose of study treatment, or is of non-childbearing potential.
Male patient agrees to use an adequate method of contraception and not donate sperm starting with the first dose of study treatment through 90 days after the last dose of study treatment. Note: Abstinence is acceptable if this is the established and preferred contraception for the patient.
Patient has measurable lesions by RECIST v1.1.
For Part A and C, in addition to the general inclusion criteria, patients must also meet the following additional criterion to be considered eligible to participate in this study:
Patient is able to take oral medications.
For patients to be eligible for any parts of the study using niraparib 300 mg as a starting dose, a screening actual body weight ≥ 77 kg and screening platelet count ≥ 150,000 u/L is necessary.
Exclusion Criteria: (Patients will not be eligible for the study entry if any of the following criteria are met)
Patient has known active central nervous system metastases, carcinomatous meningitis, or both.
Patient has a known additional malignancy that progressed or required active treatment within the last 2 years. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin that has undergone potentially curative therapy, or in situ cervical cancer.
Patient is considered a poor medical risk due to a serious, uncontrolled medical disorder, nonmalignant systemic disease, or active infection that requires systemic therapy.
Patient has a condition (such as transfusion-dependent anemia or thrombocytopenia), therapy, or laboratory abnormality that might confound the study results or interfere with the patient's participation
Patient is pregnant or expecting to conceive children within the projected duration of the study, starting with the screening visit through 180 days after the last dose of study treatment.
Note: No data are available regarding the presence of niraparib or its metabolites in human milk, or on its effects on the breastfed infant or milk production. Because of the potential for serious adverse reactions in breastfed infants from niraparib, female patients should not breastfeed during treatment with niraparib and for 1 month after receiving the final dose.
Patient has a known history of human immunodeficiency virus (type 1 or 2 antibodies).
Patient has known active hepatitis B or hepatitis C.
Patient has an active autoimmune disease that has required systemic treatment in the past 2 years.
Patient has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 including ipilimumab), or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways.
Patient has undergone prior treatment with a known PARP inhibitor.
Known history or current diagnosis of MDS or AML.
Patient has a known hypersensitivity to TSR-042 components or excipients.
For Parts B, D, E, F, G, H, and I, patients will not be eligible for study entry if any of the following additional exclusion criterion are met:
• Patient has a known hypersensitivity to any of the following relevant study treatments: carboplatin, paclitaxel, pemetrexed, nab-paclitaxel, or TSR-022 components or excipients.
For Parts C and D only, patients will not be eligible for study entry if the following additional exclusion criterion is met:
Patient has clinically significant cardiovascular disease (e.g., significant cardiac conduction abnormalities, uncontrolled hypertension, myocardial infarction, cardiac arrhythmia or unstable angina, New York Heart Association Grade 2 or greater congestive heart failure, serious cardiac arrhythmia requiring medication, Grade 2 or greater peripheral vascular disease, and history of cerebrovascular accident [CVA]) within 6 months of enrollment.
Patient has a history of bowel obstruction, including subocclusive disease, related to the underlying disease and history of abdominal fistula, gastrointestinal perforation, or intra abdominal abscesses. Evidence of recto-sigmoid involvement by pelvic examination or bowel involvement on CT scan or clinical symptoms of bowel obstruction.
Patient has proteinuria as demonstrated by urine protein: creatinine ratio ≥1.0 at screening or urine dipstick for proteinuria ≥2 (patients discovered to have ≥2 proteinuria on dipstick at baseline should undergo 24-hour urine collection and must demonstrate <2 g of protein in 24 hours to be eligible).
Patient is at increased bleeding risk due to concurrent conditions (e.g., major injuries or surgery within the past 28 days prior to start of study treatment, history of hemorrhagic stroke, transient ischemic attack, subarachnoid hemorrhage, or clinically significant hemorrhage within the past 3 months).
Patient has a known hypersensitivity to bevacizumab components or excipients.
For Parts E and F only, patients will not be eligible for study entry if any of the following additional exclusion criteria are met:
Patient is unable to interrupt aspirin or other nonsteroidal ant-inflammatory drugs, other than an aspirin dose ≤ 1.3 g per day, for a 5-day period (8-day period for long -acting agents, such as piroxicam.
Patient is unable or unwilling to take folic acid, vitamin B12 supplement.
Patient has symptomatic ascites or pleural effusion. A patient who is clinically stable following treatment for these conditions (including therapeutic thoraco- or paracentesis) is eligible.
For Parts G, H, and I only, patients will not be eligible for study entry if any of the following additional exclusion criteria are met:
• Patient has pre-existing peripheral neuropathy that is Grade ≥ 2 by Common Terminology Criteria for Adverse Events (CTCAE) version 4 criteria.
For Parts E, F, G, H and I only, patients will not be eligible for study entry if any of the following additional exclusion criteria are met:
• Patient has interstitial lung disease or a history of pneumonitis that required oral or intravenous glucocorticoids to assist with management.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
GSK Clinical Trials
Organizational Affiliation
GlaxoSmithKline
Official's Role
Study Director
Facility Information:
Facility Name
GSK Investigational Site
City
Scottsdale
State/Province
Arizona
ZIP/Postal Code
85258
Country
United States
Facility Name
GSK Investigational Site
City
Encinitas
State/Province
California
ZIP/Postal Code
92024
Country
United States
Facility Name
GSK Investigational Site
City
San Marcos
State/Province
California
ZIP/Postal Code
92069
Country
United States
Facility Name
GSK Investigational Site
City
Sarasota
State/Province
Florida
ZIP/Postal Code
34232
Country
United States
Facility Name
GSK Investigational Site
City
Canton
State/Province
Ohio
ZIP/Postal Code
44718
Country
United States
Facility Name
GSK Investigational Site
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44106
Country
United States
Facility Name
GSK Investigational Site
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37203
Country
United States
Facility Name
GSK Investigational Site
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
35332062
Citation
Yap TA, Bessudo A, Hamilton E, Sachdev J, Patel MR, Rodon J, Evilevitch L, Duncan M, Guo W, Kumar S, Lu S, Dezube BJ, Gabrail N. IOLite: phase 1b trial of doublet/triplet combinations of dostarlimab with niraparib, carboplatin-paclitaxel, with or without bevacizumab in patients with advanced cancer. J Immunother Cancer. 2022 Mar;10(3):e003924. doi: 10.1136/jitc-2021-003924.
Results Reference
background
Learn more about this trial
Study of Niraparib, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy in Combination With TSR-042
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