Back to resultsStudy to Evaluate the Efficacy and Safety of the Combination of Niraparib and Dostarlimab (TSR-042) in Participants With Platinum Resistant Ovarian Cancer (MOONSTONE)
Primary Purpose
Ovarian Neoplasms
Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Niraparib
Dostarlimab
Sponsored by
About this trial
This is an interventional treatment trial for Ovarian Neoplasms focused on measuring Open-label, Single-arm, Efficacy and Safety, Platinum-resistant ovarian cancer, Niraparib, dostarlimab
Eligibility Criteria
Inclusion criteria:
- Participant must be female >=18 years of age, able to understand the study procedures, and subsequently agreed to participate in the study by providing written informed consent.
- Participants must have recurrent high-grade serous, endometrioid, or clear cell ovarian, fallopian tube, or primary peritoneal cancer.
- Participants must be considered resistant to the last administered platinum therapy.
- Participants must have completed at least 1 but no more than 3 prior lines of therapy for advanced or metastatic ovarian cancer.
- Participants must have been previously treated with platinum-based regimen, taxane agent(s), and bevacizumab.
- Participant has measurable disease according to RECIST v.1.1.
- Participant has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
- Participant has adequate organ function.
- Females with childbearing potential have a serum pregnancy test that is negative 72 prior first dose and are not breastfeeding. Participant must also agree to abstain from activities that could result in pregnancy from enrollment through 180 days after the last dose of study treatment.
- Participant must provide formalin fixed paraffin embedded (FFPE) tumor tissue block(s) with sufficient tumor content (as confirmed by the Sponsor's designated central laboratory) during screening to enable BRCA testing and PD-L1 testing. The use of slides created from paraffin-embedded tissue as opposed to FFPE blocks must be approved by the Sponsor.
- Participant must agree to complete health-related quality of life (HRQoL) questionnaires throughout the study.
Exclusion Criteria:
- Participant who experienced disease progression within 3 months (12 weeks or 84 days) of first-line platinum therapy.
- Participants with a known deleterious or suspected BRCA 1 or 2 mutation.
- Participant has received prior therapy with an anti-PD-1, anti-PD-L1 or anti-PD-L2 agent.
- Participant has received prior therapy with a PARP-1/PARP-2 inhibitor.
- Participant has a known hypersensitivity to dostarlimab (TSR-042), Niraparib, their components, or their excipients.
- Participant has a known history of myelodysplastic syndrome or acute myeloid leukemia.
- Participant has not recovered from prior chemotherapy induced adverse events.
- Participant has a known diagnosis of immunodeficiency or is receiving systemic steroid therapy exceeding an equivalent of prednisone 10 mg daily or any other form of immunosuppressive therapy within 7 days prior to the first dose of study treatment.
- Participant is currently participating in a treatment study or has participated in a study of an investigational agent within 4 weeks of the first dose of treatment.
- Participant has received prior systemic anticancer therapy including cytotoxic chemotherapy, hormonal therapy given with the intention to treat ovarian cancer, or biological therapy within 3 weeks of the first dose of study treatment.
- Participant has received live vaccine within 14 days of planned start of study therapy
- Participant has symptomatic uncontrolled brain or leptomeningeal metastases. (If investigator feels participant symptoms are not symptomatic, participants can undergo a scan to confirm for eligibility).
- Participant had major surgery with 4 weeks of starting the first dose of the study treatment or participant has not recovered from any effects of any major surgery.
- Participant has a known additional malignancy that progressed or required active treatment within the last 2 years.
- Participant is considered a poor medical risk due to a serious, uncontrolled medical disorder, nonmalignant systemic disease or active controlled infection.
- Participant has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study.
- Participant has known active hepatitis B (hepatitis B surface antigen reactive) or hepatitis C (hepatitis C virus ribonucleic acid, qualitative).
Participant with a known history of human immunodeficiency virus (HIV) are allowed if they meet all of the following criteria:
- Cluster of differentiation 4 >=350/microliter (μL) and viral load <400 copies/milliliter (mL)
- No history of acquired immunodeficiency syndrome-defining opportunistic infections within 12 months prior to enrollment
- No history of HIV-associated malignancy for the past 5 years
- Concurrent antiretroviral therapy as per the most current National Institutes of Health (NIH) Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents Living with HIV started >4 weeks prior to study enrollment
- Participant is immunocompromised. Participants with splenectomy are allowed.
- Participant has an ongoing bowel obstruction or has other conditions that would lead to impaired absorption of oral niraparib.
- Participant has active autoimmune disease that has required systemic treatment in the past 2 years (ie, with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment.
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
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- 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 Type
Experimental
Arm Label
Niraparib+Dostarlimab (TSR-042)
Arm Description
Participants with body weight ≥77 kilogram (kg) and platelet count ≥150,000/microliter (μL) at baseline were administered Niraparib 300 milligram (mg) once daily (QD) and participants with body weight <77 kg or platelet count <150,000/μL at baseline were administered Niraparib 200 mg QD. Niraparib was administered continuously until Progressive disease (PD) or toxicity. Dostarlimab (TSR-042) was administered as an intravenous (IV) infusion of 500 mg once every three weeks (Q3W) from Cycle 1 Day 1 through Cycle 4. Beginning at Cycle 5, Dostarlimab (TSR-042) was administered via an IV infusion of 1000 mg on Day 1 of each 6-week cycle until PD or toxicity, up to 27 months.
Outcomes
Primary Outcome Measures
Objective Response Rate (ORR) in Participants With Platinum-resistant Ovarian Cancer (PROC)
ORR is defined as the percentage of participants who have achieved confirmed complete response (CR) or partial response (PR), as determined by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) criteria based on Investigator assessment and computed tomography (CT) scans were commonly used for tumor imaging.
ORR in Participants With PROC Who Have Programmed Cell Death-ligand 1 (PD-L 1) Positive Status
ORR is defined as the percentage of participants who have achieved confirmed CR or PR, as determined by RECIST v1.1 criteria based on Investigator assessment and CT scans were commonly used for tumor imaging. PD-L1 is a ligand that binds to PD-L1 protein on tumor infiltrating T cells and renders the T cells inactive. Any PD-L1 positive tissue sample with combined positive score (vCPS) >=5% was used as specified cut-point for the assessment of PD-L1 positive patient subset with PROC. vCPS was defined as the percentage of tumor cells and immune cells staining positive within the total tumor area.
Secondary Outcome Measures
Duration of Response (DOR) in Participants With PROC
DOR is defined as the time from first documentation of response (CR or PR) until the time of first documentation of disease progression or death by any cause in the absence of progression by RECIST v.1.1 based on Investigator assessment.
DOR in Participants With PROC Who Have PD-L 1 Positive Status
DOR is defined as the time from first documentation of response (CR or PR) until the time of first documentation of disease progression or death by any cause in the absence of progression by RECIST v.1.1 based on Investigator assessment. PD-L1 is a ligand that binds to PD-L1 protein on tumor infiltrating T cells and renders the T cells inactive. Any PD-L1 positive tissue sample with vCPS >=5% was used as specified cut-point for the assessment of PD-L1 patient subset with PROC. vCPS was defined as the percentage of tumor cells and immune cells staining positive within the total tumor area.
Progression-free Survival (PFS) in Participants With PROC
PFS is defined as the time from the date of the first dose of study treatment to the earlier date of assessment of progression or death by any cause in the absence of progression by RECIST v.1.1 based on Investigator assessment.
PFS in Participants With PROC Who Have PD-L 1 Positive Status
PFS is defined as the time from the date of the first dose of study treatment to the earlier date of assessment of progression or death by any cause in the absence of progression by RECIST v.1.1 based on Investigator assessment. PD-L1 is a ligand that binds to PD-L1 protein on tumor infiltrating T cells and renders the T cells inactive. Any PD-L1 positive tissue sample with a vCPS >=5% was used as specified cut-point for the assessment of PD-L1 positive patient subset with PROC. vCPS was defined as the percentage of tumor cells and immune cells staining positive within the total tumor area.
Overall Survival (OS) in Participants With PROC
OS is defined as the time from the date of the first dose of study treatment to the date of death by any cause.
OS in Participants With PROC Who Have PD-L 1 Positive Status
OS is defined as the time from the date of the first dose of study treatment to the date of death by any cause. PD-L1 is a ligand that binds to PD-L1 protein on tumor infiltrating T cells and renders the T cells inactive. Any PD-L1 positive tissue sample with vCPS >=5% was used as specified cut-point for the assessment of PD-L1 positive patient subset with PROC. vCPS was defined as the percentage of tumor cells and immune cells staining positive within the total tumor area.
Disease Control Rate (DCR) in Participants With PROC
DCR is defined as the percentage of participants who have achieved best overall response (BOR) of CR, PR, or stable disease (SD) per RECIST v.1.1 based on the investigator's assessment.
DCR in Participants With PROC Who Have PD-L 1 Positive Status
DCR is defined as the percentage of participants who have achieved BOR of CR, PR, or SD per RECIST v.1.1 based on the investigator's assessment. PD-L1 is a ligand that binds to PD-L1 protein on tumor infiltrating T cells and renders the T cells inactive. Any PD-L1 positive tissue sample with vCPS >=5% was used as specified cut-point for the assessment of PD-L1 positive patient subset with PROC. vCPS was defined as the percentage of tumor cells and immune cells staining positive within the total tumor area.
ORR in Participants With PROC Based on Independent Review Committee (IRC) Assessment
ORR is defined as the percentage of participants who have achieved confirmed CR or PR per RECIST v1.1 based on the independent review committee assessment.
ORR in Participants With PROC Who Have PD-L 1 Positive Status Based on IRC Assessment
ORR is defined as the percentage of participants who have achieved confirmed CR or PR per RECIST v1.1 based on the independent review committee assessment. PD-L1 is a ligand that binds to PD-L1 protein on tumor infiltrating T cells and renders the T cells inactive. Any PD-L1 positive tissue sample with a vCPS >=5% was used as specified cut-point for the assessment of PD-L1 positive patient subset with PROC. vCPS was defined as the percentage of tumor cells and immune cells staining positive within the total tumor area.
DOR in Participants With PROC Based on IRC Assessment
DOR is defined as the time from first documentation of response (CR or PR) until the time of first documentation of disease progression or death by any cause in the absence of progression by RECIST v.1.1 based on Independent Review Committee assessment.
DOR in Participants With PROC Who Have PD-L 1 Positive Status Based on IRC Assessment
DOR is defined as the time from first documentation of response (CR or PR) until the time of first documentation of disease progression or death by any cause in the absence of progression by RECIST v.1.1 based on Independent Review Committee assessment. PD-L1 is a ligand that binds to PD-L1 protein on tumor infiltrating T cells and renders the T cells inactive. Any PD-L1 positive tissue sample with a vCPS >=5% was used as specified cut-point for the assessment of PD-L1 positive patient subset with PROC. vCPS was defined as the percentage of tumor cells and immune cells staining positive within the total tumor area.
PFS in Participants With PROC Based on IRC Assessment
PFS is defined as the time from the date of the first dose of study treatment to the earlier date of assessment of progression or death by any cause in the absence of progression by RECIST v.1.1 based on Independent Review Committee Assessment.
PFS in Participants With PROC Who Have PD-L 1 Positive Status Based on IRC Assessment
PFS is defined as the time from the date of the first dose of study treatment to the earlier date of assessment of progression or death by any cause in the absence of progression by RECIST v.1.1 based on IRC Assessment. PD-L1 is a ligand that binds to PD-L1 protein on tumor infiltrating T cells and renders the T cells inactive. Any PD-L1 positive tissue sample with a vCPS >=5% was used as specified cut-point for the assessment of PD-L1 positive patient subset with PROC. vCPS was defined as the percentage of tumor cells and immune cells staining positive within the total tumor area.
DCR in Participants With PROC Based on IRC Assessment
DCR is defined as the percentage of participants who have achieved BOR of CR, PR, or SD per RECIST v.1.1 based on IRC Assessment.
DCR in Participants With PROC Who Have PD-L 1 Positive Status Based on IRC Assessment
DCR is defined as the percentage of participants who have achieved BOR of CR, PR, or SD per RECIST v.1.1 based on Independent Review Committee Assessment. PD-L1 is a ligand that binds to PD-L1 protein on tumor infiltrating T cells and renders the T cells inactive. Any PD-L1 positive tissue sample with vCPS >=5% was used as specified cut-point for the assessment of PD-L1 positive patient subset with PROC. vCPS was defined as the percentage of tumor cells and immune cells staining positive within the total tumor area.
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Treatment-emergent Adverse Events (TEAEs) and Adverse Event of Special Interest (AESI)
An AE is any untoward medical occurrence in a patient administered with a medicinal product and that does which may or may not have a causal relationship with this treatment. A SAE is 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 disability/incapacity, is a congenital anomaly/birth defect or any other situation according to medical or scientific judgment. TEAEs are any event that occurred between first dose of study drug up to 22 months, which were absent before treatment or that had worsened relative to pretreatment state. AESI were any AE (serious or non-serious) that is of scientific and medical concern specific to the study treatment, for which ongoing monitoring and rapid communication by the Investigator to the Sponsor was done.
Number of Participants With Grade Shift From Baseline in Hematology
Blood samples were collected for the analysis of hematology parameters and each parameter was graded according to National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events (CTCAE) version 4.3. Grade 0: Normal, Grade 1: mild; Grade 2: moderate; Grade 3: severe or medically significant; Grade 4: life-threatening consequences. Baseline was defined as the most recent measurement prior to the first administration of study treatment. Data has been presented for the number of participants with hematology grade shifts from baseline grade to grade 3 and 4 for each parameter.
Number of Participants With Grade Shift From Baseline in Plasma Chemistry
Blood samples were collected and the clinical chemistry parameters assessed were Albumin (Alb), alanine aminotransferase (ALT), amylase, aspartate aminotransferase (AST), alkaline phosphatase (ALP), sodium, total bilirubin (TB), creatinine, glucose, magnesium and potassium. The Grade shift post baseline data of each parameter from Grade 0 through Grade 4 was based on the CTCAE version 4.03, grading scale, as per intensity, namely Grade 0: Normal, Grade 1: mild; Grade 2: moderate; Grade 3: severe or medically significant; Grade 4: life-threatening consequences. Baseline was defined as the most recent measurement prior to the first administration of study treatment. Data has been presented for the number of participants with plasma chemistry grade shifts from baseline grade to grade 3 and 4 for each parameter.
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
Baseline was defined as the most recent measurement prior to the first administration of study treatment. The change from baseline was calculated by subtracting the baseline values from the individual post-randomization values. The minimum (min) and maximum (max) change from baseline values have been reported.
Change From Baseline in Pulse Rate
Baseline was defined as the most recent measurement prior to the first administration of study treatment. The change from baseline was calculated by subtracting the baseline values from the individual post-randomization values. The minimum (min) and maximum (max) change from baseline values have been reported.
Change From Baseline in Temperature
Baseline was defined as the most recent measurement prior to the first administration of study treatment. The change from baseline was calculated by subtracting the baseline values from the individual post-randomization values. The minimum (min) and maximum (max) change from baseline values have been reported.
Change From Baseline in Prothrombin International Normalized Ratio
Blood samples were collected to evaluate Prothrombin International Normalized Ratio (INR). Baseline was defined as the most recent measurement prior to the first administration of study treatment. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value.
Change in Baseline in Activated Partial Thromboplastin Time
Blood samples were planned to be collected to evaluate activated partial thromboplastin time (APTT). Baseline was defined as the most recent measurement prior to the first administration of study treatment. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value.
Change From Baseline in Thyrotropin
Blood samples were collected to evaluate thyrotropin at indicated time points. Baseline was defined as the most recent measurement prior to the first administration of study treatment. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value.
Full Information
NCT ID
NCT03955471
First Posted
May 16, 2019
Last Updated
August 16, 2022
Sponsor
Tesaro, Inc.
Collaborators
Gynecologic Oncology Group
1. Study Identification
Unique Protocol Identification Number
NCT03955471
Brief Title
Study to Evaluate the Efficacy and Safety of the Combination of Niraparib and Dostarlimab (TSR-042) in Participants With Platinum Resistant Ovarian Cancer
Acronym
MOONSTONE
Official Title
A Phase 2 Open-Label, Single-Arm Study to Evaluate the Efficacy and Safety of the Combination of Niraparib and Dostarlimab (TSR-042) in Patients With Platinum-Resistant Ovarian Cancer (MOONSTONE)
Study Type
Interventional
2. Study Status
Record Verification Date
August 2022
Overall Recruitment Status
Terminated
Why Stopped
The study will not resume based on the results of a planned interim analysis that showed futility
Study Start Date
October 3, 2019 (Actual)
Primary Completion Date
August 18, 2021 (Actual)
Study Completion Date
January 12, 2022 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Tesaro, Inc.
Collaborators
Gynecologic Oncology Group
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
This is an open-label, single-arm Phase 2 study to evaluate the efficacy and safety of combination of niraparib and dostarlimab (TSR-042) in participants with advanced, relapsed, high-grade ovarian, fallopian tube, endometrioid, clear cell ovarian or primary peritoneal cancer without known breast cancer susceptibility gene (BRCA) mutation who have platinum-resistant disease and who have also been previously treated with bevacizumab.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Ovarian Neoplasms
Keywords
Open-label, Single-arm, Efficacy and Safety, Platinum-resistant ovarian cancer, Niraparib, dostarlimab
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
41 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Niraparib+Dostarlimab (TSR-042)
Arm Type
Experimental
Arm Description
Participants with body weight ≥77 kilogram (kg) and platelet count ≥150,000/microliter (μL) at baseline were administered Niraparib 300 milligram (mg) once daily (QD) and participants with body weight <77 kg or platelet count <150,000/μL at baseline were administered Niraparib 200 mg QD. Niraparib was administered continuously until Progressive disease (PD) or toxicity. Dostarlimab (TSR-042) was administered as an intravenous (IV) infusion of 500 mg once every three weeks (Q3W) from Cycle 1 Day 1 through Cycle 4. Beginning at Cycle 5, Dostarlimab (TSR-042) was administered via an IV infusion of 1000 mg on Day 1 of each 6-week cycle until PD or toxicity, up to 27 months.
Intervention Type
Drug
Intervention Name(s)
Niraparib
Other Intervention Name(s)
ZEJULA
Intervention Description
Niraparib is a potent, orally active poly (adenosine diphosphate-ribose) polymerase (PARP)-1 and PARP2 inhibitor being developed as a treatment for participants with tumors that harbor defects in the homologous recombination deoxyribonucleic acid (DNA) repair pathway or that are driven by PARP-mediated transcription factors.
Intervention Type
Drug
Intervention Name(s)
Dostarlimab
Intervention Description
TSR-042 is a humanized monoclonal antibody that binds with high affinity to programmed cell death-1 (PD-1) resulting in inhibition of binding to programmed cell-death receptor ligands 1 and 2 (PD-L1 and PD-L2).
Primary Outcome Measure Information:
Title
Objective Response Rate (ORR) in Participants With Platinum-resistant Ovarian Cancer (PROC)
Description
ORR is defined as the percentage of participants who have achieved confirmed complete response (CR) or partial response (PR), as determined by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) criteria based on Investigator assessment and computed tomography (CT) scans were commonly used for tumor imaging.
Time Frame
Up to approximately 22 months
Title
ORR in Participants With PROC Who Have Programmed Cell Death-ligand 1 (PD-L 1) Positive Status
Description
ORR is defined as the percentage of participants who have achieved confirmed CR or PR, as determined by RECIST v1.1 criteria based on Investigator assessment and CT scans were commonly used for tumor imaging. PD-L1 is a ligand that binds to PD-L1 protein on tumor infiltrating T cells and renders the T cells inactive. Any PD-L1 positive tissue sample with combined positive score (vCPS) >=5% was used as specified cut-point for the assessment of PD-L1 positive patient subset with PROC. vCPS was defined as the percentage of tumor cells and immune cells staining positive within the total tumor area.
Time Frame
Up to approximately 22 months
Secondary Outcome Measure Information:
Title
Duration of Response (DOR) in Participants With PROC
Description
DOR is defined as the time from first documentation of response (CR or PR) until the time of first documentation of disease progression or death by any cause in the absence of progression by RECIST v.1.1 based on Investigator assessment.
Time Frame
Up to approximately 22 months
Title
DOR in Participants With PROC Who Have PD-L 1 Positive Status
Description
DOR is defined as the time from first documentation of response (CR or PR) until the time of first documentation of disease progression or death by any cause in the absence of progression by RECIST v.1.1 based on Investigator assessment. PD-L1 is a ligand that binds to PD-L1 protein on tumor infiltrating T cells and renders the T cells inactive. Any PD-L1 positive tissue sample with vCPS >=5% was used as specified cut-point for the assessment of PD-L1 patient subset with PROC. vCPS was defined as the percentage of tumor cells and immune cells staining positive within the total tumor area.
Time Frame
Up to approximately 22 months
Title
Progression-free Survival (PFS) in Participants With PROC
Description
PFS is defined as the time from the date of the first dose of study treatment to the earlier date of assessment of progression or death by any cause in the absence of progression by RECIST v.1.1 based on Investigator assessment.
Time Frame
Up to approximately 22 months
Title
PFS in Participants With PROC Who Have PD-L 1 Positive Status
Description
PFS is defined as the time from the date of the first dose of study treatment to the earlier date of assessment of progression or death by any cause in the absence of progression by RECIST v.1.1 based on Investigator assessment. PD-L1 is a ligand that binds to PD-L1 protein on tumor infiltrating T cells and renders the T cells inactive. Any PD-L1 positive tissue sample with a vCPS >=5% was used as specified cut-point for the assessment of PD-L1 positive patient subset with PROC. vCPS was defined as the percentage of tumor cells and immune cells staining positive within the total tumor area.
Time Frame
Up to approximately 22 months
Title
Overall Survival (OS) in Participants With PROC
Description
OS is defined as the time from the date of the first dose of study treatment to the date of death by any cause.
Time Frame
Up to approximately 22 months
Title
OS in Participants With PROC Who Have PD-L 1 Positive Status
Description
OS is defined as the time from the date of the first dose of study treatment to the date of death by any cause. PD-L1 is a ligand that binds to PD-L1 protein on tumor infiltrating T cells and renders the T cells inactive. Any PD-L1 positive tissue sample with vCPS >=5% was used as specified cut-point for the assessment of PD-L1 positive patient subset with PROC. vCPS was defined as the percentage of tumor cells and immune cells staining positive within the total tumor area.
Time Frame
Up to approximately 22 months
Title
Disease Control Rate (DCR) in Participants With PROC
Description
DCR is defined as the percentage of participants who have achieved best overall response (BOR) of CR, PR, or stable disease (SD) per RECIST v.1.1 based on the investigator's assessment.
Time Frame
Up to approximately 22 months
Title
DCR in Participants With PROC Who Have PD-L 1 Positive Status
Description
DCR is defined as the percentage of participants who have achieved BOR of CR, PR, or SD per RECIST v.1.1 based on the investigator's assessment. PD-L1 is a ligand that binds to PD-L1 protein on tumor infiltrating T cells and renders the T cells inactive. Any PD-L1 positive tissue sample with vCPS >=5% was used as specified cut-point for the assessment of PD-L1 positive patient subset with PROC. vCPS was defined as the percentage of tumor cells and immune cells staining positive within the total tumor area.
Time Frame
Up to approximately 22 months
Title
ORR in Participants With PROC Based on Independent Review Committee (IRC) Assessment
Description
ORR is defined as the percentage of participants who have achieved confirmed CR or PR per RECIST v1.1 based on the independent review committee assessment.
Time Frame
Up to approximately 22 months
Title
ORR in Participants With PROC Who Have PD-L 1 Positive Status Based on IRC Assessment
Description
ORR is defined as the percentage of participants who have achieved confirmed CR or PR per RECIST v1.1 based on the independent review committee assessment. PD-L1 is a ligand that binds to PD-L1 protein on tumor infiltrating T cells and renders the T cells inactive. Any PD-L1 positive tissue sample with a vCPS >=5% was used as specified cut-point for the assessment of PD-L1 positive patient subset with PROC. vCPS was defined as the percentage of tumor cells and immune cells staining positive within the total tumor area.
Time Frame
Up to approximately 22 months
Title
DOR in Participants With PROC Based on IRC Assessment
Description
DOR is defined as the time from first documentation of response (CR or PR) until the time of first documentation of disease progression or death by any cause in the absence of progression by RECIST v.1.1 based on Independent Review Committee assessment.
Time Frame
Up to approximately 22 months
Title
DOR in Participants With PROC Who Have PD-L 1 Positive Status Based on IRC Assessment
Description
DOR is defined as the time from first documentation of response (CR or PR) until the time of first documentation of disease progression or death by any cause in the absence of progression by RECIST v.1.1 based on Independent Review Committee assessment. PD-L1 is a ligand that binds to PD-L1 protein on tumor infiltrating T cells and renders the T cells inactive. Any PD-L1 positive tissue sample with a vCPS >=5% was used as specified cut-point for the assessment of PD-L1 positive patient subset with PROC. vCPS was defined as the percentage of tumor cells and immune cells staining positive within the total tumor area.
Time Frame
Up to approximately 22 months
Title
PFS in Participants With PROC Based on IRC Assessment
Description
PFS is defined as the time from the date of the first dose of study treatment to the earlier date of assessment of progression or death by any cause in the absence of progression by RECIST v.1.1 based on Independent Review Committee Assessment.
Time Frame
Up to approximately 22 months
Title
PFS in Participants With PROC Who Have PD-L 1 Positive Status Based on IRC Assessment
Description
PFS is defined as the time from the date of the first dose of study treatment to the earlier date of assessment of progression or death by any cause in the absence of progression by RECIST v.1.1 based on IRC Assessment. PD-L1 is a ligand that binds to PD-L1 protein on tumor infiltrating T cells and renders the T cells inactive. Any PD-L1 positive tissue sample with a vCPS >=5% was used as specified cut-point for the assessment of PD-L1 positive patient subset with PROC. vCPS was defined as the percentage of tumor cells and immune cells staining positive within the total tumor area.
Time Frame
Up to approximately 22 months
Title
DCR in Participants With PROC Based on IRC Assessment
Description
DCR is defined as the percentage of participants who have achieved BOR of CR, PR, or SD per RECIST v.1.1 based on IRC Assessment.
Time Frame
Up to approximately 22 months
Title
DCR in Participants With PROC Who Have PD-L 1 Positive Status Based on IRC Assessment
Description
DCR is defined as the percentage of participants who have achieved BOR of CR, PR, or SD per RECIST v.1.1 based on Independent Review Committee Assessment. PD-L1 is a ligand that binds to PD-L1 protein on tumor infiltrating T cells and renders the T cells inactive. Any PD-L1 positive tissue sample with vCPS >=5% was used as specified cut-point for the assessment of PD-L1 positive patient subset with PROC. vCPS was defined as the percentage of tumor cells and immune cells staining positive within the total tumor area.
Time Frame
Up to approximately 22 months
Title
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Treatment-emergent Adverse Events (TEAEs) and Adverse Event of Special Interest (AESI)
Description
An AE is any untoward medical occurrence in a patient administered with a medicinal product and that does which may or may not have a causal relationship with this treatment. A SAE is 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 disability/incapacity, is a congenital anomaly/birth defect or any other situation according to medical or scientific judgment. TEAEs are any event that occurred between first dose of study drug up to 22 months, which were absent before treatment or that had worsened relative to pretreatment state. AESI were any AE (serious or non-serious) that is of scientific and medical concern specific to the study treatment, for which ongoing monitoring and rapid communication by the Investigator to the Sponsor was done.
Time Frame
Up to approximately 27 months
Title
Number of Participants With Grade Shift From Baseline in Hematology
Description
Blood samples were collected for the analysis of hematology parameters and each parameter was graded according to National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events (CTCAE) version 4.3. Grade 0: Normal, Grade 1: mild; Grade 2: moderate; Grade 3: severe or medically significant; Grade 4: life-threatening consequences. Baseline was defined as the most recent measurement prior to the first administration of study treatment. Data has been presented for the number of participants with hematology grade shifts from baseline grade to grade 3 and 4 for each parameter.
Time Frame
Up to approximately 27 months
Title
Number of Participants With Grade Shift From Baseline in Plasma Chemistry
Description
Blood samples were collected and the clinical chemistry parameters assessed were Albumin (Alb), alanine aminotransferase (ALT), amylase, aspartate aminotransferase (AST), alkaline phosphatase (ALP), sodium, total bilirubin (TB), creatinine, glucose, magnesium and potassium. The Grade shift post baseline data of each parameter from Grade 0 through Grade 4 was based on the CTCAE version 4.03, grading scale, as per intensity, namely Grade 0: Normal, Grade 1: mild; Grade 2: moderate; Grade 3: severe or medically significant; Grade 4: life-threatening consequences. Baseline was defined as the most recent measurement prior to the first administration of study treatment. Data has been presented for the number of participants with plasma chemistry grade shifts from baseline grade to grade 3 and 4 for each parameter.
Time Frame
Up to approximately 27 months
Title
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
Description
Baseline was defined as the most recent measurement prior to the first administration of study treatment. The change from baseline was calculated by subtracting the baseline values from the individual post-randomization values. The minimum (min) and maximum (max) change from baseline values have been reported.
Time Frame
Up to approximately 27 months
Title
Change From Baseline in Pulse Rate
Description
Baseline was defined as the most recent measurement prior to the first administration of study treatment. The change from baseline was calculated by subtracting the baseline values from the individual post-randomization values. The minimum (min) and maximum (max) change from baseline values have been reported.
Time Frame
Up to approximately 27 months
Title
Change From Baseline in Temperature
Description
Baseline was defined as the most recent measurement prior to the first administration of study treatment. The change from baseline was calculated by subtracting the baseline values from the individual post-randomization values. The minimum (min) and maximum (max) change from baseline values have been reported.
Time Frame
Up to approximately 27 months
Title
Change From Baseline in Prothrombin International Normalized Ratio
Description
Blood samples were collected to evaluate Prothrombin International Normalized Ratio (INR). Baseline was defined as the most recent measurement prior to the first administration of study treatment. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value.
Time Frame
Baseline and up to approximately 27 months
Title
Change in Baseline in Activated Partial Thromboplastin Time
Description
Blood samples were planned to be collected to evaluate activated partial thromboplastin time (APTT). Baseline was defined as the most recent measurement prior to the first administration of study treatment. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value.
Time Frame
Baseline and up to approximately 27 months
Title
Change From Baseline in Thyrotropin
Description
Blood samples were collected to evaluate thyrotropin at indicated time points. Baseline was defined as the most recent measurement prior to the first administration of study treatment. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value.
Time Frame
Baseline and up to approximately 27 months
10. Eligibility
Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion criteria:
Participant must be female >=18 years of age, able to understand the study procedures, and subsequently agreed to participate in the study by providing written informed consent.
Participants must have recurrent high-grade serous, endometrioid, or clear cell ovarian, fallopian tube, or primary peritoneal cancer.
Participants must be considered resistant to the last administered platinum therapy.
Participants must have completed at least 1 but no more than 3 prior lines of therapy for advanced or metastatic ovarian cancer.
Participants must have been previously treated with platinum-based regimen, taxane agent(s), and bevacizumab.
Participant has measurable disease according to RECIST v.1.1.
Participant has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
Participant has adequate organ function.
Females with childbearing potential have a serum pregnancy test that is negative 72 prior first dose and are not breastfeeding. Participant must also agree to abstain from activities that could result in pregnancy from enrollment through 180 days after the last dose of study treatment.
Participant must provide formalin fixed paraffin embedded (FFPE) tumor tissue block(s) with sufficient tumor content (as confirmed by the Sponsor's designated central laboratory) during screening to enable BRCA testing and PD-L1 testing. The use of slides created from paraffin-embedded tissue as opposed to FFPE blocks must be approved by the Sponsor.
Participant must agree to complete health-related quality of life (HRQoL) questionnaires throughout the study.
Exclusion Criteria:
Participant who experienced disease progression within 3 months (12 weeks or 84 days) of first-line platinum therapy.
Participants with a known deleterious or suspected BRCA 1 or 2 mutation.
Participant has received prior therapy with an anti-PD-1, anti-PD-L1 or anti-PD-L2 agent.
Participant has received prior therapy with a PARP-1/PARP-2 inhibitor.
Participant has a known hypersensitivity to dostarlimab (TSR-042), Niraparib, their components, or their excipients.
Participant has a known history of myelodysplastic syndrome or acute myeloid leukemia.
Participant has not recovered from prior chemotherapy induced adverse events.
Participant has a known diagnosis of immunodeficiency or is receiving systemic steroid therapy exceeding an equivalent of prednisone 10 mg daily or any other form of immunosuppressive therapy within 7 days prior to the first dose of study treatment.
Participant is currently participating in a treatment study or has participated in a study of an investigational agent within 4 weeks of the first dose of treatment.
Participant has received prior systemic anticancer therapy including cytotoxic chemotherapy, hormonal therapy given with the intention to treat ovarian cancer, or biological therapy within 3 weeks of the first dose of study treatment.
Participant has received live vaccine within 14 days of planned start of study therapy
Participant has symptomatic uncontrolled brain or leptomeningeal metastases. (If investigator feels participant symptoms are not symptomatic, participants can undergo a scan to confirm for eligibility).
Participant had major surgery with 4 weeks of starting the first dose of the study treatment or participant has not recovered from any effects of any major surgery.
Participant has a known additional malignancy that progressed or required active treatment within the last 2 years.
Participant is considered a poor medical risk due to a serious, uncontrolled medical disorder, nonmalignant systemic disease or active controlled infection.
Participant has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study.
Participant has known active hepatitis B (hepatitis B surface antigen reactive) or hepatitis C (hepatitis C virus ribonucleic acid, qualitative).
Participant with a known history of human immunodeficiency virus (HIV) are allowed if they meet all of the following criteria:
Cluster of differentiation 4 >=350/microliter (μL) and viral load <400 copies/milliliter (mL)
No history of acquired immunodeficiency syndrome-defining opportunistic infections within 12 months prior to enrollment
No history of HIV-associated malignancy for the past 5 years
Concurrent antiretroviral therapy as per the most current National Institutes of Health (NIH) Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents Living with HIV started >4 weeks prior to study enrollment
Participant is immunocompromised. Participants with splenectomy are allowed.
Participant has an ongoing bowel obstruction or has other conditions that would lead to impaired absorption of oral niraparib.
Participant has active autoimmune disease that has required systemic treatment in the past 2 years (ie, with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment.
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
Duarte
State/Province
California
ZIP/Postal Code
91010
Country
United States
Facility Name
GSK Investigational Site
City
Newport Beach
State/Province
California
ZIP/Postal Code
92663
Country
United States
Facility Name
GSK Investigational Site
City
Orange
State/Province
California
ZIP/Postal Code
92868
Country
United States
Facility Name
GSK Investigational Site
City
Solvang
State/Province
California
ZIP/Postal Code
93463
Country
United States
Facility Name
GSK Investigational Site
City
Deerfield Beach
State/Province
Florida
ZIP/Postal Code
33442
Country
United States
Facility Name
GSK Investigational Site
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
Facility Name
GSK Investigational Site
City
Orlando
State/Province
Florida
ZIP/Postal Code
32804
Country
United States
Facility Name
GSK Investigational Site
City
Tampa
State/Province
Florida
ZIP/Postal Code
33612
Country
United States
Facility Name
GSK Investigational Site
City
Iowa City
State/Province
Iowa
ZIP/Postal Code
52242-1009
Country
United States
Facility Name
GSK Investigational Site
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
GSK Investigational Site
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
GSK Investigational Site
City
Burlington
State/Province
Massachusetts
ZIP/Postal Code
01805
Country
United States
Facility Name
GSK Investigational Site
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55404
Country
United States
Facility Name
GSK Investigational Site
City
Jackson
State/Province
Mississippi
ZIP/Postal Code
39216
Country
United States
Facility Name
GSK Investigational Site
City
New York
State/Province
New York
ZIP/Postal Code
10022
Country
United States
Facility Name
GSK Investigational Site
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
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
Cleveland
State/Province
Ohio
ZIP/Postal Code
44124
Country
United States
Facility Name
GSK Investigational Site
City
Eugene
State/Province
Oregon
ZIP/Postal Code
97401
Country
United States
Facility Name
GSK Investigational Site
City
Providence
State/Province
Rhode Island
ZIP/Postal Code
02905
Country
United States
Facility Name
GSK Investigational Site
City
Chattanooga
State/Province
Tennessee
ZIP/Postal Code
37403
Country
United States
Facility Name
GSK Investigational Site
City
Germantown
State/Province
Tennessee
ZIP/Postal Code
38138
Country
United States
Facility Name
GSK Investigational Site
City
Austin
State/Province
Texas
ZIP/Postal Code
78731
Country
United States
Facility Name
GSK Investigational Site
City
Fort Worth
State/Province
Texas
ZIP/Postal Code
76104
Country
United States
Facility Name
GSK Investigational Site
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229
Country
United States
Facility Name
GSK Investigational Site
City
Charlottesville
State/Province
Virginia
ZIP/Postal Code
22903
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Study to Evaluate the Efficacy and Safety of the Combination of Niraparib and Dostarlimab (TSR-042) in Participants With Platinum Resistant Ovarian Cancer
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