Adjuvant Therapy With Pembrolizumab Versus Placebo in Resected High-risk Stage II Melanoma: A Randomized, Double-blind Phase 3 Study (KEYNOTE-716)
Overview
- Phase
- Phase 3
- Intervention
- Pembrolizumab
- Conditions
- Melanoma
- Sponsor
- Merck Sharp & Dohme LLC
- Enrollment
- 976
- Locations
- 159
- Primary Endpoint
- Recurrence-free Survival (RFS)
- Status
- Active, not recruiting
- Last Updated
- last year
Overview
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
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.
Intervention: Pembrolizumab
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.
Intervention: Pembrolizumab
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.
Intervention: Placebo
Outcomes
Primary Outcomes
Recurrence-free Survival (RFS)
Time Frame: 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 Outcomes
- Distant Metastasis-free Survival (DMFS)(Up to ~9 years)
- Number of Participants Who Experienced at Least One Adverse Event (AE)(Up to ~19.3 months)
- Overall Survival (OS)(Up to ~15 years)
- Number of Participants Who Discontinued Study Treatment Due to an AE(Up to ~19.3 months)