Safety and Efficacy of Pembrolizumab Compared to Placebo in Resected High-risk Stage II Melanoma (MK-3475-716/KEYNOTE-716)
- Registration Number
- NCT03553836
- Lead Sponsor
- Merck Sharp & Dohme LLC
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 976
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Pembrolizumab Pembrolizumab Participants receive 200 mg pembrolizumab (2 mg/kg for a maximum of 200 mg in pediatric participants) by intravenous (IV) infusion once every 3 weeks (Q3W; 21-day cycles) for up to 17 cycles (up to \~1 year) in Part 1. Participants who complete the initial treatment of 17 cycles of pembrolizumab 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. Placebo Pembrolizumab Participants receive saline placebo by IV infusion Q3W (21-day cycles) for up to 17 cycles (up to \~1 year) in Part 1. Participants who complete the initial treatment of 17 cycles 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. Placebo Placebo Participants receive saline placebo by IV infusion Q3W (21-day cycles) for up to 17 cycles (up to \~1 year) in Part 1. Participants who complete the initial treatment of 17 cycles 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.
- Primary Outcome Measures
Name Time Method Recurrence-free Survival (RFS) Up to ~32.7 months 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.
- Secondary Outcome Measures
Name Time Method Distant Metastasis-free Survival (DMFS) Up to ~9 years 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.
Number of Participants Who Experienced at Least One Adverse Event (AE) Up to ~19.3 months 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.
Overall Survival (OS) Up to ~15 years OS will be defined as the time from randomization to death due to any cause. OS will be reported for randomized participants.
Number of Participants Who Discontinued Study Treatment Due to an AE Up to ~19.3 months 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.
Trial Locations
- Locations (159)
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
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
Scroll for more (149 remaining)University of Arizona Cancer Center ( Site 0121)🇺🇸Tucson, Arizona, United States