Back to resultsA Study Of Avelumab In Combination With Axitinib In Advanced Renal Cell Cancer (JAVELIN Renal 100)
Primary Purpose
Renal Cell Cancer
Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
Avelumab (MSB0010718C)
Axitinib (AG-013736)
Sponsored by
About this trial
This is an interventional treatment trial for Renal Cell Cancer focused on measuring Cancer, renal cell cancer, kidney disease, kidney neoplasms, axitinib
Eligibility Criteria
Inclusion Criteria:
- Histologically or cytologically confirmed advanced RCC with clear cell component
- Primary tumor resected
- Availability of a recent formalin-fixed, paraffin-embedded (FFPE) tumor tissue block from a de novo tumor biopsy during screening (biopsied tumor lesion should not be a RECIST target lesion). Alternatively, a recently obtained archival FFPE tumor tissue block (not cut slides) from a primary or metastatic tumor resection or biopsy can be provided if the following criteria are met: 1) the biopsy or resection was performed within 1 year of enrollment AND 2) the patient has not received any intervening systemic anti-cancer treatment from the time the tissue was obtained and enrollment onto the current study. If an FFPE tissue block cannot be provided as per documented regulations,, 15 unstained slides (10 minimum) will be acceptable.
- Availability of an archival FFPE tumor tissue block from primary diagnosis specimen (if available and not provided per above). If an FFPE tissue block cannot be provided, 15 unstained slides (10 minimum) will be acceptable
- At least one measureable lesion as defined by RECIST version 1.1 that has not been previously irradiated.
- Age ≥18 years (≥ 20 years in Japan).
- Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
- Adequate bone marrow function, renal and liver functions
Exclusion Criteria:
- Prior systemic therapy directed at advanced RCC.
- Prior adjuvant or neoadjuvant therapy for RCC if disease progression or relapse has occurred during or within 12 months after the last dose of treatment
- Prior immunotherapy with IL-2, IFN-α, or anti PD 1, anti PD L1, anti PD L2, anti CD137, or anti cytotoxic T lymphocyte associated antigen 4 (CTLA 4) antibody (including ipilimumab), or any other antibody or drug specifically targeting T cell co stimulation or immune checkpoint pathways
- Prior therapy with axitinib as well as any prior therapies with other VEGF pathway inhibitors.
- Known severe hypersensitivity reactions to monoclonal antibodies (Grade ≥3), any history of anaphylaxis.
- Any of the following in the previous 6 months: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident, transient ischemic attack, deep vein thrombosis or symptomatic pulmonary embolism.
- Vaccination within 4 weeks of the first dose of avelumab and while on trial is prohibited except for administration of inactivated vaccines (for example, inactivated influenza vaccines).
Sites / Locations
- Scottsdale Healthcare Hospitals d/b/a HonorHealth
- Georgetown University Medical Center
- Brigham & Women's Hospital
- Beth Israel Deaconess Medical Center
- Dana Farber Cancer Institute
- Laura & Isaac Perlmutter Cancer Center At NYU Langone
- NYU Langone Medical Center
- Cleveland Clinic Taussig Cancer Center
- Cleveland Clinic
- Henry Joyce Cancer Clinic
- University of Utah, Huntsman Cancer Hospital
- University of Utah, Huntsman Cancer Institute
- Niigata University Medical & Dental Hospital
- Kindai University Hospital
- Keio University Hospital
- Mount Vernon Cancer Center, East and North Herts. NHS Trust
- St Helier Hospital
- St. Bartholomew's Hospital
- The Royal Marsden NHS Foundation Trust
- The Christie NHS Foundation Trust
- The Royal Marsden NHS Foundation Trust
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Dose finding phase and dose expansion phase.
Arm Description
To test the maximum tolerated dose of avelumab (MSB0010718C) in combination with axitinib (AG-013736)
Outcomes
Primary Outcome Measures
Number of Participants With Dose Limiting Toxicities (DLTs)
DLT: greater than or equal to (>=) Grade 3 hematologic/non-hematologic toxicity, Grade 3-4 liver-related laboratory test elevation (alanine aminotransferase, aspartate aminotransferase) with Grade 2 elevation of total bilirubin, non-hematologic Grade 3 laboratory abnormality (required medical intervention to treat participant/led to hospitalization), inability to complete >=75% of first 2 cycles doses of axitinib (from Cycle 1 Day 1 after completion of lead-in period) or 2 infusions of avelumab within DLT observation period due to investigational product related toxicity.
Secondary Outcome Measures
Number of Participants With All-causality Treatment Emergent Adverse Events (TEAEs)
Adverse event (AE)=any untoward medical occurrence in participant who received study treatment without regard to causality. TEAE=event between first dose of study treatment and up to 30 days after last dose that were absent before treatment or worsened relative to pretreatment state. Serious AE (SAE)=AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience; persistent or significant disability/incapacity; congenital anomaly. AEs were graded by worst National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 severity grade. Grade 3 event=unacceptable or intolerable event, significantly interrupting usual daily activity, require systemic drug therapy/other treatment. Grade 4 event caused participant to be in imminent danger of death. Grade 5 event=death related to AE. The results reflect data available on cutoff of LPLV (04 Mar 2021).
Number of Participants With Treatment-related TEAEs
Treatment-related AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. TEAE=event between first dose of study treatment and up to 30 days after last dose that were absent before treatment or that worsened relative to pretreatment state. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience; persistent or significant disability/incapacity; congenital anomaly. AEs were graded by worst NCI CTCAE v4.03 severity grade. Grade 3 events=unacceptable or intolerable events, significantly interrupting usual daily activity, require systemic drug therapy/other treatment. Grade 4 events caused participant to be in imminent danger of death. Grade 5 events=death related to an AE. Treatment-related AEs and SAEs were determined by the investigator. The results reflect data available on cutoff of LPLV (04 Mar 2021).
Number of Participants With Laboratory Abnormalities Graded by NCI CTCAE Version 4.03 - Hematology
Laboratory abnormalities (hematology) reported included anemia, platelet count decreased, lymphocyte count decreased, and neutrophil count decreased. Grade 1=mild transient reaction; infusion interruption not indicated; intervention not indicated. Grade 2=therapy or infusion interruption indicated but responds promptly to symptomatic treatment; prophylactic medications indicated for <=24 hours. Grade 3=prolonged; recurrence of symptoms following initial improvement; hospitalization indicated for clinical sequelae. Grade 4=life threatening consequences; urgent intervention indicated. Grade 5=death. The results reflect data available on cutoff of LPLV (04 Mar 2021).
Number of Participants With Laboratory Abnormalities Graded by NCI CTCAE Version 4.03 - Chemistry
Laboratory abnormalities (chemistry) reported included creatinine increased, serum amylase increased, lipase increased, alanine aminotransferase (ALT) increased, aspartate aminotransferase (AST) increased, blood bilirubin increased, creatine kinase increased, hypoglycemia, and hyperglycemia. Grade 1=mild transient reaction; infusion interruption not indicated; intervention not indicated. Grade 2=therapy or infusion interruption indicated but responds promptly to symptomatic treatment; prophylactic medications indicated for <=24 hours. Grade 3=prolonged; recurrence of symptoms following initial improvement; hospitalization indicated for clinical sequelae. Grade 4=life threatening consequences; urgent intervention indicated. Grade 5=death. The results reflect data available on cutoff of LPLV (04 Mar 2021).
Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure
Blood pressure was taken with the participant in the seated position after the participant had been sitting quietly for at least 5 minutes. Baseline was defined as the last assessment prior to the date/time of the first dose of study treatment, which occurred on Day 1 in Lead-in period for participants with lead-in, and occurred on Cycle 1 Day 1 (C1D1) for participants without lead-in. The results reflect data available on cutoff of primary completion date (PCD) (03 Apr 2018).
Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure
Blood pressure was taken with the participant in the seated position after the participant had been sitting quietly for at least 5 minutes. Baseline was defined as the last assessment prior to the date/time of the first dose of study treatment, which occurred on Day 1 in Lead-in period for participants with lead-in, and occurred on Cycle 1 Day 1 (C1D1) for participants without lead-in. The results reflect data available on cutoff of PCD (03 Apr 2018).
Change From Baseline in Vital Signs - Pulse Rate
Pulse rate was taken with the participant in the seated position after the participant had been sitting quietly for at least 5 minutes. Baseline was defined as the last assessment prior to the date/time of the first dose of study treatment, which occurred on Day 1 in Lead-in period for participants with lead-in, and occurred on Cycle 1 Day 1 (C1D1) for participants without lead-in. The results reflect data available on cutoff of PCD (03 Apr 2018).
Number of Participants Achieving Objective Response (OR) Based on Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
Confirmed OR was defined as complete response (CR) or partial response (PR) according to RECIST v1.1 from the start date until disease progression or death due to any cause. CR was defined as complete disappearance of all target lesions with the exception of nodal disease. All target nodes must decrease to normal size (short axis <10 mm). PR was defined as >= 30% decrease under baseline of the sum of diameters of all target measurable lesions. The short diameter was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. All target lesions must have been assessed. The results reflect data available on cutoff of PCD (03 Apr 2018).
Number of Participants Achieving Disease Control (DC) Based on RECIST Version 1.1
DC was defined as OR (CR or PR) or stable disease (SD) per RECIST v1.1 from the start date until the first documentation of objective disease progression or death due to any cause. SD was defined as not qualifying for CR, PR, or progression (PD). PD was defined as 20% increase in the sum of diameters of target measurable lesions above the smallest sum observed (over baseline if no decrease in the sum was observed during therapy), with a minimum absolute increase of 5 mm. CR was defined as complete disappearance of all target lesions with the exception of nodal disease. All target nodes must decrease to normal size (short axis <10 mm). PR was defined as >= 30% decrease under baseline of the sum of diameters of all target measurable lesions. The short diameter was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. All target lesions must have been assessed. The results reflect data available on cutoff of PCD (03 Apr 2018).
Duration of Response (DR) Based on RECIST Version 1.1
DR was defined as the time from the first documentation of objective tumor response (CR or PR) that was subsequently confirmed to the first documentation of objective tumor progression or to death due to any cause, whichever occurred first. CR was defined as complete disappearance of all target lesions with the exception of nodal disease. All target nodes must decrease to normal size (short axis <10 mm). PR was defined as >= 30% decrease under baseline of the sum of diameters of all target measurable lesions. The short diameter was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. All target lesions must have been assessed. The results reflect data available on cutoff of PCD (03 Apr 2018).
Progression-free Survival (PFS)
PFS was defined as defined as the time from the start date to the date of the first documentation of objective progression of disease (PD) or death due to any cause, whichever occurred first. PD was defined as 20% increase in the sum of diameters of target measurable lesions above the smallest sum observed (over baseline if no decrease in the sum was observed during therapy), with a minimum absolute increase of 5 mm. All target lesions must have been assessed. The results reflect data available on cutoff of PCD (03 Apr 2018).
Time to Tumor Response (TTR) Based on RECIST Version 1.1
TTR was defined as the time from start date to the first documentation of objective tumor response (CR or PR) that was subsequently confirmed. CR was defined as complete disappearance of all target lesions with the exception of nodal disease. All target nodes must decrease to normal size (short axis <10 mm). PR was defined as >= 30% decrease under baseline of the sum of diameters of all target measurable lesions. The short diameter was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. All target lesions must have been assessed. The results reflect data available on cutoff of PCD (03 Apr 2018).
Overall Survival (OS)
OS was defined as the time from the start date to the date of death due to any cause. The results reflect data available on cutoff of PCD (03 Apr 2018).
Maximum Observed Plasma Concentration (Cmax) for Axitinib When Dosed Alone and in Combination With Avelumab
Cmax for axitinib when dosed alone on Lead-in Day 7 and in combination with avelumab on Cycle 4 Day 1 for Axitinib + Avelumab with Lead-in Arm. The results reflect data available on cutoff of PCD (03 Apr 2018).
Time for Cmax (Tmax) for Axitinib When Dosed Alone and in Combination With Avelumab
Tmax for axitinib when dosed alone on Lead-in Day 7 and in combination with avelumab on Cycle 4 Day 1 for Axitinib + Avelumab with Lead-in Arm. The results reflect data available on cutoff of PCD (03 Apr 2018).
Area Under the Plasma Concentration Time Profile From Time Zero to the Next Dose at Steady State (AUCtau) for Axitinib When Dosed Alone and in Combination With Avelumab
AUCtau was defined as area under the plasma concentration time profile from time zero to time tau, the dosing interval at steady state. tau = 12 hrs for Axitinib. AUCtau for Axitinib when dosed alone on Lead-in Day 7 and in combination with avelumab on Cycle 4 Day 1 for Axitinib + Avelumab with Lead-in Arm was reported. The results reflect data available on cutoff of PCD (03 Apr 2018).
Terminal Half-Life (t1/2) for Axitinib When Dosed Alone and in Combination With Avelumab
t1/2 was calculated by Log e(2)/kel. kel was the terminal phase rate constant calculated by a linear regression of the log linear concentration time-curve. Only those data points judged to describe the terminal log linear decline were used in the regression. t1/2 for Axitinib when dosed alone on Lead-in Day 7 and in combination with avelumab on Cycle 4 Day 1 for Axitinib + Avelumab with Lead-in Arm was reported. The results reflect data available on cutoff of PCD (03 Apr 2018).
Predose Concentration During Multiple Dosing (Ctrough) for Avelumab
Ctrough was directly observed from data. The results reflect data available on cutoff of PCD (03 Apr 2018).
Cmax for Avelumab
Cmax for avelumab on Cycle 1 Day (C1D1) and C1D4 were reported. The results reflect data available on cutoff of PCD (03 Apr 2018).
Number of Participants With Their Target Programmed Death-Ligand (PD-L1) Status at Baseline
Number of participants with PD-L1 positive (PD-L1 >=1%) status in immune cell (IC), tumor cell (TC), or both IC and TC. The results reflect data available on cutoff of PCD (03 Apr 2018).
Number of Participants With Anti-drug Antibody (ADA) Against Avelumab When Combined With Axitinib by Never and Ever Positive Status
Whole blood specimens were collected at the designated times (Day 1 of Cycles 1-4, 6, and 8, then every 12 weeks until Cycle 50, and Follow-up Day 30) to provide serum for evaluation of avelumab immunogenicity. Human serum ADA specimens were analyzed for the presence or absence of anti-avelumab antibodies with quasi-quantitative enzyme-linked immunosorbent assay, following a tiered approach using screening, confirmation and titer/quantitation. ADA serum specimens were screened at tier 1. In the event that there were no positive specimens, no further analyses were to be conducted. If positive specimens were identified, these specimens were further tested with the confirmatory assay to confirm as positive. Number of participants with ADA positive at baseline, ADA never-positive, ADA ever-positive, treatment-boosted ADA, treatment-induced ADA, transient ADA response, or persistent ADA response from baseline up to 2 years. The results reflect data available on cutoff of PCD (03 Apr 2018).
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02493751
Brief Title
A Study Of Avelumab In Combination With Axitinib In Advanced Renal Cell Cancer (JAVELIN Renal 100)
Official Title
A PHASE 1B, OPEN-LABEL, DOSE-FINDING STUDY TO EVALUATE SAFETY, PHARMACOKINETICS AND PHARMACODYNAMICS OF AVELUMAB (MSB0010718C) IN COMBINATION WITH AXITINIB (AG-013736) IN PATIENTS WITH PREVIOUSLY UNTREATED ADVANCED RENAL CELL CANCER
Study Type
Interventional
2. Study Status
Record Verification Date
December 2021
Overall Recruitment Status
Completed
Study Start Date
October 26, 2015 (Actual)
Primary Completion Date
April 3, 2018 (Actual)
Study Completion Date
March 4, 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Pfizer
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
This is a Phase 1b, open-label, multi-center, multiple-dose trial designed to estimate the maximum tolerated dose (MTD) and select the recommended phase 2 dose (RP2D) of avelumab (MSB0010718C) in combination with axitinib (AG-013736). Once the MTD of avelumab administered in combination with axitinib is estimated (dose finding portion), the dose expansion phase will be opened to further characterize the combination in term of safety profile, anti tumor activity, pharmacokinetics, pharmacodynamics and biomarker modulation.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Renal Cell Cancer
Keywords
Cancer, renal cell cancer, kidney disease, kidney neoplasms, axitinib
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Masking
None (Open Label)
Allocation
N/A
Enrollment
55 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Dose finding phase and dose expansion phase.
Arm Type
Experimental
Arm Description
To test the maximum tolerated dose of avelumab (MSB0010718C) in combination with axitinib (AG-013736)
Intervention Type
Drug
Intervention Name(s)
Avelumab (MSB0010718C)
Intervention Description
Avelumab with two dose levels: 10 mg/kg IV and 5 mg/kg IV every two weeks to find the maximum tolerated dose in combination with axitinib and continue treatment in a dose expansion.
Intervention Type
Drug
Intervention Name(s)
Axitinib (AG-013736)
Intervention Description
Axitinib with two dose levels: 5 mg and 3 mg oral BID to find the maximum tolerated dose in combination with avelumab and continue treatment in a dose expansion.
Primary Outcome Measure Information:
Title
Number of Participants With Dose Limiting Toxicities (DLTs)
Description
DLT: greater than or equal to (>=) Grade 3 hematologic/non-hematologic toxicity, Grade 3-4 liver-related laboratory test elevation (alanine aminotransferase, aspartate aminotransferase) with Grade 2 elevation of total bilirubin, non-hematologic Grade 3 laboratory abnormality (required medical intervention to treat participant/led to hospitalization), inability to complete >=75% of first 2 cycles doses of axitinib (from Cycle 1 Day 1 after completion of lead-in period) or 2 infusions of avelumab within DLT observation period due to investigational product related toxicity.
Time Frame
DLT observation period (from the beginning of Cycle 1 up to the end of Cycle 2 [28 days])
Secondary Outcome Measure Information:
Title
Number of Participants With All-causality Treatment Emergent Adverse Events (TEAEs)
Description
Adverse event (AE)=any untoward medical occurrence in participant who received study treatment without regard to causality. TEAE=event between first dose of study treatment and up to 30 days after last dose that were absent before treatment or worsened relative to pretreatment state. Serious AE (SAE)=AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience; persistent or significant disability/incapacity; congenital anomaly. AEs were graded by worst National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 severity grade. Grade 3 event=unacceptable or intolerable event, significantly interrupting usual daily activity, require systemic drug therapy/other treatment. Grade 4 event caused participant to be in imminent danger of death. Grade 5 event=death related to AE. The results reflect data available on cutoff of LPLV (04 Mar 2021).
Time Frame
Baseline up to 30 days after the last dose of study treatment (maximum of 259.7 weeks)
Title
Number of Participants With Treatment-related TEAEs
Description
Treatment-related AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. TEAE=event between first dose of study treatment and up to 30 days after last dose that were absent before treatment or that worsened relative to pretreatment state. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience; persistent or significant disability/incapacity; congenital anomaly. AEs were graded by worst NCI CTCAE v4.03 severity grade. Grade 3 events=unacceptable or intolerable events, significantly interrupting usual daily activity, require systemic drug therapy/other treatment. Grade 4 events caused participant to be in imminent danger of death. Grade 5 events=death related to an AE. Treatment-related AEs and SAEs were determined by the investigator. The results reflect data available on cutoff of LPLV (04 Mar 2021).
Time Frame
Baseline up to 30 days after the last dose of study treatment (maximum of 259.7 weeks)
Title
Number of Participants With Laboratory Abnormalities Graded by NCI CTCAE Version 4.03 - Hematology
Description
Laboratory abnormalities (hematology) reported included anemia, platelet count decreased, lymphocyte count decreased, and neutrophil count decreased. Grade 1=mild transient reaction; infusion interruption not indicated; intervention not indicated. Grade 2=therapy or infusion interruption indicated but responds promptly to symptomatic treatment; prophylactic medications indicated for <=24 hours. Grade 3=prolonged; recurrence of symptoms following initial improvement; hospitalization indicated for clinical sequelae. Grade 4=life threatening consequences; urgent intervention indicated. Grade 5=death. The results reflect data available on cutoff of LPLV (04 Mar 2021).
Time Frame
Baseline up to 30 days after the last dose of study treatment and 1 day before the start day of new anti-cancer drug therapy (maximum of 259.7 weeks)
Title
Number of Participants With Laboratory Abnormalities Graded by NCI CTCAE Version 4.03 - Chemistry
Description
Laboratory abnormalities (chemistry) reported included creatinine increased, serum amylase increased, lipase increased, alanine aminotransferase (ALT) increased, aspartate aminotransferase (AST) increased, blood bilirubin increased, creatine kinase increased, hypoglycemia, and hyperglycemia. Grade 1=mild transient reaction; infusion interruption not indicated; intervention not indicated. Grade 2=therapy or infusion interruption indicated but responds promptly to symptomatic treatment; prophylactic medications indicated for <=24 hours. Grade 3=prolonged; recurrence of symptoms following initial improvement; hospitalization indicated for clinical sequelae. Grade 4=life threatening consequences; urgent intervention indicated. Grade 5=death. The results reflect data available on cutoff of LPLV (04 Mar 2021).
Time Frame
Baseline up to 30 days after the last dose of study treatment and 1 day before the start day of new anti-cancer drug therapy (maximum of 259.7 weeks)
Title
Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure
Description
Blood pressure was taken with the participant in the seated position after the participant had been sitting quietly for at least 5 minutes. Baseline was defined as the last assessment prior to the date/time of the first dose of study treatment, which occurred on Day 1 in Lead-in period for participants with lead-in, and occurred on Cycle 1 Day 1 (C1D1) for participants without lead-in. The results reflect data available on cutoff of primary completion date (PCD) (03 Apr 2018).
Time Frame
Baseline, Day 1 of each cycle, Day 8 of Cycles 1 and 2, end of treatment, Follow-up Days 30, 60, 90 for all participants in the analysis population, and Lead-in Day 7 for participants with lead-in (maximum of 139.6 weeks by PCD)
Title
Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure
Description
Blood pressure was taken with the participant in the seated position after the participant had been sitting quietly for at least 5 minutes. Baseline was defined as the last assessment prior to the date/time of the first dose of study treatment, which occurred on Day 1 in Lead-in period for participants with lead-in, and occurred on Cycle 1 Day 1 (C1D1) for participants without lead-in. The results reflect data available on cutoff of PCD (03 Apr 2018).
Time Frame
Baseline, Day 1 of each cycle, Day 8 of Cycles 1 and 2, end of treatment, Follow-up Days 30, 60, 90 for all participants in the analysis population, and Lead-in Day 7 for participants with lead-in (maximum of 139.6 weeks by PCD)
Title
Change From Baseline in Vital Signs - Pulse Rate
Description
Pulse rate was taken with the participant in the seated position after the participant had been sitting quietly for at least 5 minutes. Baseline was defined as the last assessment prior to the date/time of the first dose of study treatment, which occurred on Day 1 in Lead-in period for participants with lead-in, and occurred on Cycle 1 Day 1 (C1D1) for participants without lead-in. The results reflect data available on cutoff of PCD (03 Apr 2018).
Time Frame
Baseline, Day 1 of each cycle, Day 8 of Cycles 1 and 2, end of treatment, Follow-up Days 30, 60, 90 for all participants in the analysis population, and Lead-in Day 7 for participants with lead-in (maximum of 139.6 weeks by PCD)
Title
Number of Participants Achieving Objective Response (OR) Based on Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
Description
Confirmed OR was defined as complete response (CR) or partial response (PR) according to RECIST v1.1 from the start date until disease progression or death due to any cause. CR was defined as complete disappearance of all target lesions with the exception of nodal disease. All target nodes must decrease to normal size (short axis <10 mm). PR was defined as >= 30% decrease under baseline of the sum of diameters of all target measurable lesions. The short diameter was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. All target lesions must have been assessed. The results reflect data available on cutoff of PCD (03 Apr 2018).
Time Frame
Cycle 1 Day 1 up to 30 months after the first dose
Title
Number of Participants Achieving Disease Control (DC) Based on RECIST Version 1.1
Description
DC was defined as OR (CR or PR) or stable disease (SD) per RECIST v1.1 from the start date until the first documentation of objective disease progression or death due to any cause. SD was defined as not qualifying for CR, PR, or progression (PD). PD was defined as 20% increase in the sum of diameters of target measurable lesions above the smallest sum observed (over baseline if no decrease in the sum was observed during therapy), with a minimum absolute increase of 5 mm. CR was defined as complete disappearance of all target lesions with the exception of nodal disease. All target nodes must decrease to normal size (short axis <10 mm). PR was defined as >= 30% decrease under baseline of the sum of diameters of all target measurable lesions. The short diameter was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. All target lesions must have been assessed. The results reflect data available on cutoff of PCD (03 Apr 2018).
Time Frame
Cycle 1 Day 1 up to 30 months after the first dose
Title
Duration of Response (DR) Based on RECIST Version 1.1
Description
DR was defined as the time from the first documentation of objective tumor response (CR or PR) that was subsequently confirmed to the first documentation of objective tumor progression or to death due to any cause, whichever occurred first. CR was defined as complete disappearance of all target lesions with the exception of nodal disease. All target nodes must decrease to normal size (short axis <10 mm). PR was defined as >= 30% decrease under baseline of the sum of diameters of all target measurable lesions. The short diameter was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. All target lesions must have been assessed. The results reflect data available on cutoff of PCD (03 Apr 2018).
Time Frame
Cycle 1 Day 1 up to 30 months after the first dose
Title
Progression-free Survival (PFS)
Description
PFS was defined as defined as the time from the start date to the date of the first documentation of objective progression of disease (PD) or death due to any cause, whichever occurred first. PD was defined as 20% increase in the sum of diameters of target measurable lesions above the smallest sum observed (over baseline if no decrease in the sum was observed during therapy), with a minimum absolute increase of 5 mm. All target lesions must have been assessed. The results reflect data available on cutoff of PCD (03 Apr 2018).
Time Frame
Cycle 1 Day 1 up to 30 months after the first dose
Title
Time to Tumor Response (TTR) Based on RECIST Version 1.1
Description
TTR was defined as the time from start date to the first documentation of objective tumor response (CR or PR) that was subsequently confirmed. CR was defined as complete disappearance of all target lesions with the exception of nodal disease. All target nodes must decrease to normal size (short axis <10 mm). PR was defined as >= 30% decrease under baseline of the sum of diameters of all target measurable lesions. The short diameter was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. All target lesions must have been assessed. The results reflect data available on cutoff of PCD (03 Apr 2018).
Time Frame
Cycle 1 Day 1 up to 30 months after the first dose
Title
Overall Survival (OS)
Description
OS was defined as the time from the start date to the date of death due to any cause. The results reflect data available on cutoff of PCD (03 Apr 2018).
Time Frame
Cycle 1 Day 1 up to 30 months after the first dose
Title
Maximum Observed Plasma Concentration (Cmax) for Axitinib When Dosed Alone and in Combination With Avelumab
Description
Cmax for axitinib when dosed alone on Lead-in Day 7 and in combination with avelumab on Cycle 4 Day 1 for Axitinib + Avelumab with Lead-in Arm. The results reflect data available on cutoff of PCD (03 Apr 2018).
Time Frame
Predose, 1, 2, 3, 4, 6, and 8 hours post dose on Lead-in Day 7 and Cycle 4 Day 1
Title
Time for Cmax (Tmax) for Axitinib When Dosed Alone and in Combination With Avelumab
Description
Tmax for axitinib when dosed alone on Lead-in Day 7 and in combination with avelumab on Cycle 4 Day 1 for Axitinib + Avelumab with Lead-in Arm. The results reflect data available on cutoff of PCD (03 Apr 2018).
Time Frame
Predose, 1, 2, 3, 4, 6, and 8 hours post dose on Lead-in Day 7 and Cycle 4 Day 1
Title
Area Under the Plasma Concentration Time Profile From Time Zero to the Next Dose at Steady State (AUCtau) for Axitinib When Dosed Alone and in Combination With Avelumab
Description
AUCtau was defined as area under the plasma concentration time profile from time zero to time tau, the dosing interval at steady state. tau = 12 hrs for Axitinib. AUCtau for Axitinib when dosed alone on Lead-in Day 7 and in combination with avelumab on Cycle 4 Day 1 for Axitinib + Avelumab with Lead-in Arm was reported. The results reflect data available on cutoff of PCD (03 Apr 2018).
Time Frame
Predose, 1, 2, 3, 4, 6, and 8 hours post dose on Lead-in Day 7 and Cycle 4 Day 1
Title
Terminal Half-Life (t1/2) for Axitinib When Dosed Alone and in Combination With Avelumab
Description
t1/2 was calculated by Log e(2)/kel. kel was the terminal phase rate constant calculated by a linear regression of the log linear concentration time-curve. Only those data points judged to describe the terminal log linear decline were used in the regression. t1/2 for Axitinib when dosed alone on Lead-in Day 7 and in combination with avelumab on Cycle 4 Day 1 for Axitinib + Avelumab with Lead-in Arm was reported. The results reflect data available on cutoff of PCD (03 Apr 2018).
Time Frame
Predose, 1, 2, 3, 4, 6, and 8 hours post dose on Lead-in Day 7 and Cycle 4 Day 1
Title
Predose Concentration During Multiple Dosing (Ctrough) for Avelumab
Description
Ctrough was directly observed from data. The results reflect data available on cutoff of PCD (03 Apr 2018).
Time Frame
Predose on Day 1 of Cycles 1, 2, 3, 4, 6, 8, 14, 20, 26, 32, 38, 44, and 50
Title
Cmax for Avelumab
Description
Cmax for avelumab on Cycle 1 Day (C1D1) and C1D4 were reported. The results reflect data available on cutoff of PCD (03 Apr 2018).
Time Frame
Predose, 1 hour, and 168 hours post dose on Cycle 1 Day 1; predose and 1 hour post dose on Cycle 4 Day 1
Title
Number of Participants With Their Target Programmed Death-Ligand (PD-L1) Status at Baseline
Description
Number of participants with PD-L1 positive (PD-L1 >=1%) status in immune cell (IC), tumor cell (TC), or both IC and TC. The results reflect data available on cutoff of PCD (03 Apr 2018).
Time Frame
Baseline
Title
Number of Participants With Anti-drug Antibody (ADA) Against Avelumab When Combined With Axitinib by Never and Ever Positive Status
Description
Whole blood specimens were collected at the designated times (Day 1 of Cycles 1-4, 6, and 8, then every 12 weeks until Cycle 50, and Follow-up Day 30) to provide serum for evaluation of avelumab immunogenicity. Human serum ADA specimens were analyzed for the presence or absence of anti-avelumab antibodies with quasi-quantitative enzyme-linked immunosorbent assay, following a tiered approach using screening, confirmation and titer/quantitation. ADA serum specimens were screened at tier 1. In the event that there were no positive specimens, no further analyses were to be conducted. If positive specimens were identified, these specimens were further tested with the confirmatory assay to confirm as positive. Number of participants with ADA positive at baseline, ADA never-positive, ADA ever-positive, treatment-boosted ADA, treatment-induced ADA, transient ADA response, or persistent ADA response from baseline up to 2 years. The results reflect data available on cutoff of PCD (03 Apr 2018).
Time Frame
Pre-dose on Day 1 of Cycles 1-4, 6, 8, then every 12 weeks thereafter until Cycle 50, and on Follow-up Day 30 (maximum of 2 years)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Histologically or cytologically confirmed advanced RCC with clear cell component
Primary tumor resected
Availability of a recent formalin-fixed, paraffin-embedded (FFPE) tumor tissue block from a de novo tumor biopsy during screening (biopsied tumor lesion should not be a RECIST target lesion). Alternatively, a recently obtained archival FFPE tumor tissue block (not cut slides) from a primary or metastatic tumor resection or biopsy can be provided if the following criteria are met: 1) the biopsy or resection was performed within 1 year of enrollment AND 2) the patient has not received any intervening systemic anti-cancer treatment from the time the tissue was obtained and enrollment onto the current study. If an FFPE tissue block cannot be provided as per documented regulations,, 15 unstained slides (10 minimum) will be acceptable.
Availability of an archival FFPE tumor tissue block from primary diagnosis specimen (if available and not provided per above). If an FFPE tissue block cannot be provided, 15 unstained slides (10 minimum) will be acceptable
At least one measureable lesion as defined by RECIST version 1.1 that has not been previously irradiated.
Age ≥18 years (≥ 20 years in Japan).
Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
Adequate bone marrow function, renal and liver functions
Exclusion Criteria:
Prior systemic therapy directed at advanced RCC.
Prior adjuvant or neoadjuvant therapy for RCC if disease progression or relapse has occurred during or within 12 months after the last dose of treatment
Prior immunotherapy with IL-2, IFN-α, or anti PD 1, anti PD L1, anti PD L2, anti CD137, or anti cytotoxic T lymphocyte associated antigen 4 (CTLA 4) antibody (including ipilimumab), or any other antibody or drug specifically targeting T cell co stimulation or immune checkpoint pathways
Prior therapy with axitinib as well as any prior therapies with other VEGF pathway inhibitors.
Known severe hypersensitivity reactions to monoclonal antibodies (Grade ≥3), any history of anaphylaxis.
Any of the following in the previous 6 months: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident, transient ischemic attack, deep vein thrombosis or symptomatic pulmonary embolism.
Vaccination within 4 weeks of the first dose of avelumab and while on trial is prohibited except for administration of inactivated vaccines (for example, inactivated influenza vaccines).
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Pfizer CT.gov Call Center
Organizational Affiliation
Pfizer
Official's Role
Study Director
Facility Information:
Facility Name
Scottsdale Healthcare Hospitals d/b/a HonorHealth
City
Scottsdale
State/Province
Arizona
ZIP/Postal Code
85258
Country
United States
Facility Name
Georgetown University Medical Center
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20007
Country
United States
Facility Name
Brigham & Women's Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
Beth Israel Deaconess Medical Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
Dana Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
Laura & Isaac Perlmutter Cancer Center At NYU Langone
City
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States
Facility Name
NYU Langone Medical Center
City
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States
Facility Name
Cleveland Clinic Taussig Cancer Center
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44106
Country
United States
Facility Name
Cleveland Clinic
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
Facility Name
Henry Joyce Cancer Clinic
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232-5310
Country
United States
Facility Name
University of Utah, Huntsman Cancer Hospital
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84112
Country
United States
Facility Name
University of Utah, Huntsman Cancer Institute
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84112
Country
United States
Facility Name
Niigata University Medical & Dental Hospital
City
Chuo-ku, Niigata
State/Province
Niigata
ZIP/Postal Code
951-8520
Country
Japan
Facility Name
Kindai University Hospital
City
Osakasayama
State/Province
Osaka
ZIP/Postal Code
589-8511
Country
Japan
Facility Name
Keio University Hospital
City
Shinjuku-ku
State/Province
Tokyo
ZIP/Postal Code
160-8582
Country
Japan
Facility Name
Mount Vernon Cancer Center, East and North Herts. NHS Trust
City
London
State/Province
Middlesex
ZIP/Postal Code
HA6 2RN
Country
United Kingdom
Facility Name
St Helier Hospital
City
Carshalton
State/Province
Surrey
ZIP/Postal Code
SM5 1AA
Country
United Kingdom
Facility Name
St. Bartholomew's Hospital
City
London
ZIP/Postal Code
EC1A 7BE
Country
United Kingdom
Facility Name
The Royal Marsden NHS Foundation Trust
City
London
ZIP/Postal Code
SW3 6JJ
Country
United Kingdom
Facility Name
The Christie NHS Foundation Trust
City
Manchester
ZIP/Postal Code
M20 4BX
Country
United Kingdom
Facility Name
The Royal Marsden NHS Foundation Trust
City
Sutton
ZIP/Postal Code
SM2 5PT
Country
United Kingdom
12. IPD Sharing Statement
Plan to Share IPD
No
IPD Sharing Plan Description
Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.
Citations:
PubMed Identifier
35166465
Citation
Masters JC, Khandelwal A, di Pietro A, Dai H, Brar S. Model-informed drug development supporting the approval of the avelumab flat-dose regimen in patients with advanced renal cell carcinoma. CPT Pharmacometrics Syst Pharmacol. 2022 Apr;11(4):458-468. doi: 10.1002/psp4.12771. Epub 2022 Feb 27.
Results Reference
derived
PubMed Identifier
33947608
Citation
Rini BI, Atkins MB, Choueiri TK, Thomaidou D, Rosbrook B, Thakur M, Hutson TE. Time to Resolution of Axitinib-Related Adverse Events After Treatment Interruption in Patients With Advanced Renal Cell Carcinoma. Clin Genitourin Cancer. 2021 Oct;19(5):e306-e312. doi: 10.1016/j.clgc.2021.03.019. Epub 2021 Apr 5.
Results Reference
derived
PubMed Identifier
29530667
Citation
Choueiri TK, Larkin J, Oya M, Thistlethwaite F, Martignoni M, Nathan P, Powles T, McDermott D, Robbins PB, Chism DD, Cho D, Atkins MB, Gordon MS, Gupta S, Uemura H, Tomita Y, Compagnoni A, Fowst C, di Pietro A, Rini BI. Preliminary results for avelumab plus axitinib as first-line therapy in patients with advanced clear-cell renal-cell carcinoma (JAVELIN Renal 100): an open-label, dose-finding and dose-expansion, phase 1b trial. Lancet Oncol. 2018 Apr;19(4):451-460. doi: 10.1016/S1470-2045(18)30107-4. Epub 2018 Mar 9.
Results Reference
derived
Links:
URL
https://trialinfoemail.pfizer.com/pages/landing.aspx?StudyID=B9991002&StudyName=A%20Phase%201b%2C%20Open-label%2C%20Dose-finding%20Study%20To%20Evaluate%20Safety%2C%0Apharmacokinetics%20And%20Pharmacodynamics%20Of%20Avelumab%0A%28msb0010718c%29%20In%20Combination%20With%20Axitinib%20%28ag-013736%29%20In%20Patients%0Awith%20Previously%20Untreated%20Advanced%20Renal%20Cell%20Cancer
Description
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Learn more about this trial
A Study Of Avelumab In Combination With Axitinib In Advanced Renal Cell Cancer (JAVELIN Renal 100)
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