This 2-part study will evaluate the safety and efficacy of pembrolizumab (MK-3475) compared to placebo in participants with surgically resected high-risk Stage II melanoma. Participants in Part 1 will receive either pembrolizumab or placebo in a double-blind design every 3 weeks (Q3W) for up to 17 cycles/\~1 year (each cycle = 21 days). Participants who complete the initial treatment of 17 cycles of pembrolizumab in Part 1 and experience disease recurrence may be eligible for re-challenge with pembrolizumab at the same dose and schedule of 200 mg Q3W (21-day cycles) for up to 35 cycles (up to \~2 years) in Part 2 in an open label design. Participants who complete the initial treatment of placebo and experience disease recurrence may be eligible to switch over to pembrolizumab 200 mg Q3W (21-day cycles) for up to 35 cycles (up to \~2 years) in Part 2 in an open label design. The primary hypothesis of this study is that pembrolizumab increases recurrence-free survival (RFS) compared to placebo. Per protocol, response/ progression or adverse events (AEs) during re-challenge/switch-over in Part 2 will not be counted towards the RFS outcome measure or safety outcome measures respectively.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
976
Administered as an intravenous (IV) infusion every 3 weeks (Q3W)
Administered as an IV infusion every 3 weeks (Q3W)
University of Arizona Cancer Center ( Site 0121)
Tucson, Arizona, United States
UCSD Moores Cancer Center ( Site 0133)
La Jolla, California, United States
The Angeles Clinic and Research Institute ( Site 0029)
Los Angeles, California, United States
UCLA Hematology & Oncology ( Site 0130)
Los Angeles, California, United States
John Wayne Cancer Institute ( Site 0026)
Santa Monica, California, United States
Recurrence-free Survival (RFS)
RFS was defined as the time from randomization to any of the following events: recurrence of melanoma at any site (local, in-transit or regional lymph nodes or distant recurrence) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) or death due to any cause, whichever occurs first. Per protocol, final analysis for this primary outcome measure was performed using the initial pembrolizumab or placebo treatment with a protocol-specified analysis data cut-off date of June-21-2021.
Time frame: Up to ~32.7 months
Distant Metastasis-free Survival (DMFS)
DMFS will be defined as the time from randomization to the first diagnosis of a distant metastasis per RECIST 1.1. Distant metastasis will refer to cancer that has spread from the original (primary) tumor and beyond local tissues and lymph nodes to distant organs or distant lymph nodes. DMFS will be reported for randomized participants.
Time frame: Up to ~9 years
Overall Survival (OS)
OS will be defined as the time from randomization to death due to any cause. OS will be reported for randomized participants.
Time frame: Up to ~15 years
Number of Participants Who Experienced at Least One Adverse Event (AE)
An AE was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. Per protocol, analysis for this outcome measure was performed using the initial pembrolizumab or placebo treatment.
Time frame: Up to ~19.3 months
Number of Participants Who Discontinued Study Treatment Due to an AE
An AE was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. Per protocol, analysis for this outcome measure was performed using the initial pembrolizumab or placebo treatment.
Time frame: Up to ~19.3 months
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University of Colorado Cancer Center ( Site 0027)
Aurora, Colorado, United States
Yale University ( Site 0035)
New Haven, Connecticut, United States
Mayo Clinic Florida ( Site 0024)
Jacksonville, Florida, United States
Moffitt McKinley Outpatient Center ( Site 0131)
Tampa, Florida, United States
Winship Cancer Institute of Emory University ( Site 0046)
Atlanta, Georgia, United States
...and 149 more locations