Substudy 02C 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 02C is to evaluate the safety and efficacy of investigational treatment arms in participants with Stage III melanoma who are candidates for neoadjuvant therapy to identify the investigational agent(s) that, when used in combination, are superior to the current treatment options/historical control available. Arm 1: Pembrolizumab + Vibostolimab, Arm 2: Pembrolizumab + Gebasaxturev, and Arm 3: Pembrolizumab were added in the base protocol on 13-Nov-2019, and enrollment into those arms has been completed. Arm 4: Pembrolizumab + MK-4830 was added in Amendment 04 on 20-Dec-2021, and enrollment into that arm has been completed. Arm 5: Favezelimab + Pembrolizumab and Arm 6: Pembrolizumab + all-trans retinoic acid (ATRA) were added in Amendment 06 on 25-Jun-2022, and enrollment is ongoing.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
146
Administered via IV infusion at a specified dose on specified days
Administered via IV infusion at a specified dose on specified days
Administered via IT injection 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
The Angeles Clinic and Research Institute ( Site 3009)
Los Angeles, California, United States
Providence Saint John's Health Center ( Site 3010)
Santa Monica, California, United States
University of Colorado, Anschutz Cancer Pavilion ( Site 3012)
Aurora, Colorado, United States
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins ( Site 3022)
Baltimore, Maryland, United States
NYU Clinical Cancer Center ( Site 3002)
New York, New York, United States
Percentage of Participants Who Experienced an Adverse Event (AE)
An AE is 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 was reported.
Time frame: Up to approximately 17 months
Percentage of Participants Who Discontinued Study Intervention Due to an AE
An AE is 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 intervention due to an AE was reported.
Time frame: Up to approximately 13 months
Pathological Complete Response (pCR) Rate With 90% Confidence Interval (CI)
pCR rate was defined as the percentage of participants with complete absence of viable tumor in the treated tumor bed as assessed by central review of the pathology results. Per protocol, pCR rate with 90% CI was reported.
Time frame: Up to approximately 6 weeks
pCR Rate With 95% CI
pCR rate was defined as the percentage of participants with complete absence of viable tumor in the treated tumor bed as assessed by central review of the pathology results. Per protocol, pCR rate with 95% CI was reported.
Time frame: Up to approximately 6 weeks
Near pCR Rate With 90% CI
Near pCR was defined as the percentage of participants with \>0% but ≤10% of viable tumor cells in the treated tumor bed as assessed by central review of the pathology results. Per protocol, near pCR rate with 90% CI was reported.
Time frame: Up to approximately 6 weeks
Near pCR Rate With 95% CI
Near pCR was defined as the percentage of participants with \>0% but ≤10% of viable tumor cells in the treated tumor bed as assessed by central review of the pathology results. Per protocol, near pCR rate with 95% CI was reported.
Time frame: Up to approximately 6 weeks
Pathological Partial Response (pPR) Rate With 90% CI
pPR rate was defined as the percentage of participants with \>10% but ≤50% of the treated tumor bed occupied by viable tumor cells as assessed by central review of the pathology results. Per protocol, pPR rate with 90% CI was reported.
Time frame: Up to approximately 6 weeks
pPR Rate With 95% CI
pPR rate was defined as the percentage of participants with \>10% but ≤50% of the treated tumor bed occupied by viable tumor cells as assessed by central review of the pathology results. Per protocol, pPR rate with 95% CI was reported.
Time frame: Up to approximately 6 weeks
Recurrence-Free Survival (RFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by The Investigator
RFS was defined as the time from the date of surgery to (1) any recurrence (local, regional, or distant) per RECIST 1.1 as assessed by the investigator or (2) death due to any cause (both cancer and noncancer causes of death). Per protocol, RECIST 1.1 was modified to allow up to 10 target lesions total (up to 5 per organ). Per protocol, RFS per RECIST 1.1 as assessed by the investigator was presented.
Time frame: Up to approximately 62 months
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Duke Cancer Institute ( Site 3005)
Durham, North Carolina, United States
Martha Morehouse Tower ( Site 3020)
Columbus, Ohio, United States
Oregon Health & Science University ( Site 3013)
Portland, Oregon, United States
University of Pennsylvania Abramson Cancer Center ( Site 3008)
Philadelphia, Pennsylvania, United States
West Cancer Center - East Campus ( Site 3014)
Germantown, Tennessee, United States
...and 19 more locations