This study is a substudy being conducted under one pembrolizumab umbrella master study KEYMAKER-U04. The substudy will consist of 2 parts. Part 1 will evaluate the efficacy and safety of coformulated favezelimab/pembrolizumab plus EV and coformulated vibostolimab/pembrolizumab plus EV relative to pembrolizumab plus EV. There will be no comparison of coformulated favezelimab/pembrolizumab plus EV versus coformulated vibostolimab/pembrolizumab plus EV. If ORR and/or DRR are substantially better on coformulated favezelimab/pembrolizumab plus EV and/or coformulated vibostolimab/pembrolizumab plus EV compared with pembrolizumab plus EV, after evaluation of the totality of data, the sponsor might consider Part 2 (expansion) to further characterize the efficacy and safety of the treatment arms under study.
The master study for this substudy is MK-3475-U04/KEYMAKER-U04. The master study will not be screening any participants and will not be registered. With Amendment 2, participants will discontinue treatment with coformulated vibostolimab/pembrolizumab (Arm B) and be transitioned to pembrolizumab only. Per protocol, no analysis of Part 2 primary or secondary outcome measures (including efficacy or safety) will occur since Part 2 of the study will no longer take place.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
390
Coformulated favezelimab/pembrolizumab (800 mg/200 mg) IV infusion
Coformulated vibostolimab/pembrolizumab (200 mg/200 mg) IV infusion
1.25 mg/kg IV infusion
200 mg IV infusion
Moores Cancer Center ( Site 3028)
La Jolla, California, United States
University of California, Irvine (UCI) Health - UC Irvine Medical Center ( Site 3045)
Orange, California, United States
UCSF Medical Center at Mission Bay ( Site 3044)
San Francisco, California, United States
Anschutz Cancer Pavilion ( Site 3017)
Aurora, Colorado, United States
Emory University School of Medicine ( Site 3043)
Atlanta, Georgia, United States
Part 1: Objective Response Rate (ORR)
ORR is defined as the percentage of participants who achieve a confirmed complete response (CR) or partial response (PR) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 as assessed by blinded independent central review (BICR). ORR will be reported for participants in Part 1.
Time frame: Up to ~4 years
Part 1: Percentage of Participants experiencing an Adverse Event (AE)
An AE is defined as any untoward medical occurrence in a participant administered study drug, which does not necessarily have to have a causal relationship with the study drug. The number of participants experiencing an AE in Part 1 will be reported.
Time frame: Up to ~4 years
Part 1: Percentage of Participants who Discontinue study interventions due to an AE
An AE is defined as any untoward medical occurrence in a participant administered study drug, which does not necessarily have to have a causal relationship with the study drug. The number of participants who discontinue study interventions due to an AE in Part 1 will be reported.
Time frame: Up to ~4 years
Part 1: Percentage of Participants with Dose-limiting toxicities (DLT)
A DLT is defined as an event with toxicity including the type, severity, time of onset, time of resolution, and the probable association with study treatment that are not due to pre-existing conditions as defined by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events, Version 5.0 (CTCAE 5.0). The number of participants who experience a DLT in Part 1 will be reported.
Time frame: Up to 21 days
Part 2: Progression Free Survival (PFS)
PFS is defined as the time from randomization to the first documented disease progression per RECIST 1.1 by BICR or death due to any cause, whichever occurs first. PFS will be reported for participants in Part 2.
Time frame: Up to ~4 years
Part 1: PFS
PFS is defined as the time from randomization to the first documented disease progression per RECIST 1.1 by BICR or death due to any cause, whichever occurs first. PFS will be reported for participants in Part 1.
Time frame: Up to ~4 years
Part 1: Duration of Response (DOR)
For participants who demonstrate confirmed CR or PR, DOR is defined as the time from the first documented evidence of CR or PR until disease progression or death due to any cause, whichever occurs first. DOR will be reported for participants in Part 1.
Time frame: Up to ~4 years
Part 2: Overall Survival (OS)
OS is defined as the time from randomization to death due to any cause. OS will be reported for participants in Part 2.
Time frame: Up to ~4 years
Part 2: ORR
ORR is defined as the percentage of participants who achieve a confirmed CR or PR per RECIST 1.1 as assessed by BICR. ORR will be reported for participants in Part 2.
Time frame: Up to ~4 years
Part 2: DOR
For participants who demonstrate confirmed CR or PR, DOR is defined as the time from the first documented evidence of CR or PR until disease progression or death due to any cause, whichever occurs first. DOR will be reported for participants in Part 2.
Time frame: Up to ~4 years
Part 2: Percentage of Participants experiencing an Adverse Event (AE)
An AE is defined as any untoward medical occurrence in a participant administered study drug, which does not necessarily have to have a causal relationship with the study drug. The number of participants experiencing an AE in Part 2 will be reported.
Time frame: Up to ~4 years
Part 2: Percentage of Participants who Discontinue study interventions due to an AE
An AE is defined as any untoward medical occurrence in a participant administered study drug, which does not necessarily have to have a causal relationship with the study drug. The number of participants who discontinue study interventions due to an AE in Part 2 will be reported.
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Indiana University Melvin and Bren Simon Cancer Center ( Site 3011)
Indianapolis, Indiana, United States
Dana-Farber Cancer Institute ( Site 3047)
Boston, Massachusetts, United States
Siteman Cancer Center ( Site 3038)
St Louis, Missouri, United States
Icahn School of Medicine at Mount Sinai ( Site 3018)
New York, New York, United States
Memorial Sloan Kettering Cancer Center ( Site 3031)
New York, New York, United States
...and 37 more locations
Time frame: Up to ~4 years
Part 2: Percentage of Participants with Dose-limiting toxicities (DLT)
A DLT is defined as an event with toxicity including the type, severity, time of onset, time of resolution, and the probable association with study treatment that are not due to pre-existing conditions as defined by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events, Version 5.0 (CTCAE 5.0). The number of participants who experience a DLT in Part 2 will be reported.
Time frame: Up to 21 days
Part 1: Mean Change from baseline in the global health status/quality of life of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLC-C30) (Items 29 and 30)
Participants are asked to answer questions 29 and 30 from the EORTC QLC-C30. Questions 29 and 30 use a 7-point scale (1=very poor to 7=excellent) to evaluate overall health and quality of life. Scores were transformed to a range of 0 to 100 using a standard EORTC algorithm. Negative change from baseline values indicated deterioration in health status or functioning and positive changes indicated improvement. The mean change from baseline will be reported for Part 1.
Time frame: Baseline and up to ~4 years
Part 1: Mean Change from baseline in the physical functioning scale of the EORTC QLQ-C30
Participants are asked to answer questions about their physical functioning from the EORTC QLC-C30. These questions use a 4-point scale (1=not at all to 4=very much) to evaluate overall health and quality of life. Scores were transformed to a range of 0 to 100 using a standard EORTC algorithm. Negative change from baseline values indicated deterioration in health status or functioning and positive changes indicated improvement. The mean change from baseline will be reported for Part 1.
Time frame: Baseline and up to ~4 years
Part 1: Mean Change from Baseline in the European Quality of Life 5 Dimensions, 5-level Questionnaire (EQ-5D-5L) visual analog score (VAS)
The EQ-5D-5L is a descriptive five-dimensional system of evaluation. The five dimensions are mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Participants rate each dimension on 5 levels ranging from 1 (no problems) to 5 (extreme problems). The EQ-5D-5L also includes a graded (0 to 100) vertical visual analog scale on which the participant rates their general state of health. Negative change from baseline values indicated deterioration in health status or functioning and positive changes indicated improvement. The mean change from baseline will be reported for Part 1.
Time frame: Baseline and up to ~4 years
Part 2: Mean Change from baseline in the global health status/quality of life of the EORTC QLC-C30 (Items 29 and 30)
Participants are asked to answer questions 29 and 30 from the EORTC QLC-C30. Questions 29 and 30 use a 7-point scale (1=very poor to 7=excellent) to evaluate overall health and quality of life. Scores were transformed to a range of 0 to 100 using a standard EORTC algorithm. Negative change from baseline values indicated deterioration in health status or functioning and positive changes indicated improvement. The mean change from baseline will be reported for Part 2.
Time frame: Baseline and up to ~4 years
Part 2: Mean Change from baseline in the physical functioning scale of the EORTC QLQ-C30
Participants are asked to answer questions about their physical functioning from the EORTC QLC-C30. These questions use a 4-point scale (1=not at all to 4=very much) to evaluate overall health and quality of life. Scores were transformed to a range of 0 to 100 using a standard EORTC algorithm. Negative change from baseline values indicated deterioration in health status or functioning and positive changes indicated improvement. The mean change from baseline will be reported for Part 2.
Time frame: Baseline and up to ~4 years
Part 2: Mean Change from Baseline in the EQ-5D-5L visual analog score (VAS)
The EQ-5D-5L is a descriptive five-dimensional system of evaluation. The five dimensions are mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Participants rate each dimension on 5 levels ranging from 1 (no problems) to 5 (extreme problems). The EQ-5D-5L also includes a graded (0 to 100) vertical visual analog scale on which the participant rates their general state of health. Negative change from baseline values indicated deterioration in health status or functioning and positive changes indicated improvement. The mean change from baseline will be reported for Part 2.
Time frame: Baseline and up to ~4 years
Part 1: Time-to-Deterioration (TTD) for the global health status/quality of life of the EORTC QLQ-C30 (Items 29 and 30)
Participants are asked to answer questions 29 and 30 from the EORTC QLC-C30. Questions 29 and 30 use a 7-point scale (1=very poor to 7=excellent) to evaluate overall health and quality of life. Scores were transformed to a range of 0 to 100 using a standard EORTC algorithm. TTD is defined as the time from the first GHS/QoL assessment to deterioration (defined as ≥10-point decrease in GHS/QoL score from baseline) or death, whichever occurs first. The TTD in GHS/QoL score of participants will be reported for Part 1.
Time frame: Up to ~4 years
Part 1: TTD for the physical functioning scale of the EORTC QLQ-C30
Participants are asked to answer questions about their physical functioning from the EORTC QLC-C30. These questions use a 4-point scale (1=not at all to 4=very much) to evaluate overall health and quality of life. Scores were transformed to a range of 0 to 100 using a standard EORTC algorithm. Negative change from baseline values indicated deterioration in health status or functioning and positive changes indicated improvement. TTD is defined as the time from the first GHS/QoL assessment to deterioration (defined as ≥10-point decrease in GHS/QoL score from baseline) or death, whichever occurs first. The TTD in GHS/QoL score of participants will be reported for Part 1.
Time frame: Up to ~4 years
Part 1: TTD for the EQ-5D-5L VAS
The EQ-5D-5L is a descriptive five-dimensional system of evaluation. The five dimensions are mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Participants rate each dimension on 5 levels ranging from 1 (no problems) to 5 (extreme problems). The EQ-5D-5L also includes a graded (0 to 100) vertical visual analog scale on which the participant rates their general state of health. Negative change from baseline values indicated deterioration in health status or functioning and positive changes indicated improvement. TTD is defined as the time from the first EQ-5D-5L VAS assessment to deterioration (defined as ≥7-point decrease in EQ-5D-5L VAS score more from baseline) or death, whichever occurs first. The TTD in EQ-5D-5L VAS score of participants will be reported for Part 1.
Time frame: Up to ~4 years
Part 2: TTD for the global health status/quality of life of the EORTC QLQ-C30 (Items 29 and 30)
Participants are asked to answer questions 29 and 30 from the EORTC QLC-C30. Questions 29 and 30 use a 7-point scale (1=very poor to 7=excellent) to evaluate overall health and quality of life. Scores were transformed to a range of 0 to 100 using a standard EORTC algorithm. TTD is defined as the time from the first GHS/QoL assessment to deterioration (defined as ≥10-point decrease in GHS/QoL score from baseline) or death, whichever occurs first. The TTD in GHS/QoL score of participants will be reported for Part 2.
Time frame: Up to ~4 years
Part 2: TTD for the physical functioning scale of the EORTC QLQ-C30
Participants are asked to answer questions about their physical functioning from the EORTC QLC-C30. These questions use a 4-point scale (1=not at all to 4=very much) to evaluate overall health and quality of life. Scores were transformed to a range of 0 to 100 using a standard EORTC algorithm. Negative change from baseline values indicated deterioration in health status or functioning and positive changes indicated improvement. TTD is defined as the time from the first GHS/QoL assessment to deterioration (defined as ≥10-point decrease in GHS/QoL score from baseline) or death, whichever occurs first. The TTD in GHS/QoL score of participants will be reported for Part 2.
Time frame: Up to ~4 years
Part 2: TTD for the EQ-5D-5L VAS
The EQ-5D-5L is a descriptive five-dimensional system of evaluation. The five dimensions are mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Participants rate each dimension on 5 levels ranging from 1 (no problems) to 5 (extreme problems). The EQ-5D-5L also includes a graded (0 to 100) vertical visual analog scale on which the participant rates their general state of health. Negative change from baseline values indicated deterioration in health status or functioning and positive changes indicated improvement. TTD is defined as the time from the first EQ-5D-5L VAS assessment to deterioration (defined as ≥7-point decrease in EQ-5D-5L VAS score more from baseline) or death, whichever occurs first. The TTD in EQ-5D-5L VAS score of participants will be reported for Part 2.
Time frame: Up to ~4 years