A Phase 2 interventional study of Pembrolizumab and Ipilimumab plus nivolumab in Melanoma (Skin Cancer), Melanoma Stage Stage IIIB and Melanoma Stage M1, sponsored by UNC Lineberger Comprehensive Cancer Center. Recruiting at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-09-30.
Sponsored by UNC Lineberger Comprehensive Cancer Center · Phase 2, Interventional, and Treatment
This study evaluates the impact of neoadjuvant Programmed cell death Protein 1 (PD-1)-based treatment regimens in patients with resectable stage IIIB-M1a cutaneous or unknown primary melanoma at high risk of relapse without adjuvant therapy after definitive lymphadenectomy and irrespective of pathologic response outcome on the 2-year overall survival (OS). It was hypothesized that neoadjuvant PD1 inhibitor-based treatment without adjuvant treatment does not significantly (non-inferior) impact OS in this study patient population. Patients will be randomized to either two infusions of pembrolizumab or one infusion of ipilimumab plus nivolumab followed by a single infusion of nivolumab. Patients will undergo follow-up and restaging scans to assess event-free survival at 12 months and OS at 24 months after the first neoadjuvant treatment infusion.
Exclusion Criteria:
Participants receive pembrolizumab 200 mg IV, every 3 weeks, times 2 infusions followed by lymph node dissection, followed by no adjuvant treatment.
Drug: Pembrolizumab
Participants receive ipilimumab (3 mg/kg) plus nivolumab (1 mg/kg) x one infusion, followed by a single infusion of nivolumab 240 mg IV 3 weeks later, followed by lymph node dissection, followed by no adjuvant treatment
Drug: Ipilimumab plus nivolumab
Pembrolizumab 200 mg IV, every 3 weeks
Single infusion of concurrent ipilimumab (3 mg/kg) plus nivolumab (1 mg/kg) followed by a single infusion of nivolumab 240 mg IV 3 weeks later
Overall survival
The overall survival (OS) rate will be defined from the initiation of study treatments for the combined patient cohorts (cohort A and cohort B).
Time frame: 2-year
Event - Free Survival (EFS)
The Event - Free Survival (EFS) rate will be defined from the initiation of study treatments for the combined patient cohorts (cohort A and cohort B).
Time frame: 1-year
Major pathologic response (MPR) rate
The MPR rate for each of the two study treatment cohorts (cohort A and cohort B) will be defined using established pathologic response criteria. Pathologic response will be assessed by determining the percentage of residual viable tumor in the resected specimen. Major pathologic response is defined as ≤10% residual viable tumor, and pathologic complete response is defined as the absence of viable tumor cells.
Time frame: Up to 12 weeks
Treatment Related Adverse Events (TRAEs)
TRAEs are defined as adverse events assessed by the investigator as related to study treatment, Grade 3 or higher grades. The incidence of TRAEs will be determined separately for each of the two cohorts and graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 6.0. CTCAE classifies severity as follows: Grade 1 - asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2 - minimal, local, or noninvasive intervention indicated; limiting age-appropriate instrumental activities of daily living (ADL). Grade 3 - severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care ADL. Grade 4 - life-threatening consequences; urgent intervention indicated. Grade 5 - death related to the adverse event.
Time frame: Up to 12 weeks
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UNC Lineberger Comprehensive Cancer Center