Substudy 02A is part of a larger research study that is testing experimental treatments for melanoma, a type of skin cancer. The larger study is the umbrella study. The goal of substudy 02A is to evaluate the safety and efficacy of investigational treatment arms in participants with PD-1 refractory melanoma to identify the investigational agent(s) that, when used in combination, are superior to the current treatment options/historical control available. As of Amendment 4 (effective date: 05JAN2022), a third arm has been opened to participant enrollment, treatment with pembrolizumab and all-trans retinoic acid (ATRA). Enrollment into the first two arms, treatment with pembrolizumab + quavonlimab+ vibostolimab and treatment with pembrolizumab + quavonlimab + lenvatinib has been completed per protocol as of September 2021.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
100
Administered via IV infusion at a specified dose on specified days
Administered via IV infusion at a specified dose on specified days
Administered via IV infusion at a specified dose on specified days
Administered via oral capsules at a specified dose on specified days
Administered via oral capsules at a specified dose on specified days
The Angeles Clinic and Research Institute ( Site 1009)
Los Angeles, California, United States
UCLA Hematology & Oncology ( Site 1004)
Los Angeles, California, United States
Providence Saint John's Health Center ( Site 1010)
Santa Monica, California, United States
University of Colorado, Anschutz Cancer Pavilion ( Site 1012)
Aurora, Colorado, United States
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins ( Site 1022)
Baltimore, Maryland, United States
Percentage of Participants Who Experienced an Adverse Event (AE)
An AE was any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The percentage of participants who experienced an AE is reported.
Time frame: Up to approximately 39 months
Percentage of Participants Who Discontinued Study Treatment Due to an AE
An AE was any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The percentage of participants who discontinued study treatment due to an AE is reported.
Time frame: Up to 35 months
Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1) With 95% Confidence Interval (CI)
ORR was defined as the percentage of participants in the analysis population who have a complete response (CR: disappearance of all target lesions) or partial response (PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters). Responses are according to RECIST 1.1 as assessed by blinded independent central review (BICR). RECIST 1.1 was modified for this study to include a maximum of 10 target lesions and a maximum of 5 target lesions per organ. Per protocol, ORR with 95% CI was reported.
Time frame: Up to approximately 59 months
ORR Per RECIST 1.1 With 90% CI
ORR was defined as the percentage of participants in the analysis population who have a complete response (CR: disappearance of all target lesions) or partial response (PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters). Responses are according to RECIST 1.1 as assessed by BICR. RECIST 1.1 was modified for this study to include a maximum of 10 target lesions and a maximum of 5 target lesions per organ. Per protocol, ORR with 90% CI was reported.
Time frame: Up to approximately 59 months
Duration of Response (DOR) Per RECIST 1.1
For participants in the analysis population who showed a confirmed CR (disappearance of all target lesions) or confirmed PR (at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters), DOR was defined as the time from first documented evidence of CR or PR until progressive disease (PD) or death due to any cause, whichever occurred first. Responses were according to RECIST 1.1 as assessed by BICR. RECIST 1.1 was modified for this study to include a maximum of 10 target lesions and a maximum of 5 target lesions per organ.
Time frame: Up to approximately 59 months
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NYU Clinical Cancer Center ( Site 1002)
New York, New York, United States
Duke Cancer Institute ( Site 1005)
Durham, North Carolina, United States
Martha Morehouse Tower ( Site 1020)
Columbus, Ohio, United States
Oregon Health & Science University ( Site 1013)
Portland, Oregon, United States
University of Pennsylvania Abramson Cancer Center ( Site 1008)
Philadelphia, Pennsylvania, United States
...and 26 more locations