Phase 2 NASA tests pembrolizumab PD‑1 blockade vs ipilimumab CTLA‑4 + nivolumab PD‑1 in resectable melanoma.

This randomized Phase 2 study at UNC Lineberger Comprehensive Cancer Center asks whether a short neoadjuvant checkpoint regimen can safely replace the usual months-long postoperative (adjuvant) systemic therapy in resectable stage IIIB–IV (M1a) cutaneous or unknown-primary melanoma. Patients are assigned to either pembrolizumab (Merck/MSD), a PD‑1 (CD279)–blocking monoclonal antibody given every 3 weeks for 2 doses, or to ipilimumab (Bristol Myers Squibb), a CTLA‑4–blocking monoclonal antibody, plus nivolumab (Bristol Myers Squibb), a PD‑1–blocking monoclonal antibody, followed by a second nivolumab dose 3 weeks later; all then undergo definitive lymphadenectomy with no planned adjuvant therapy regardless of pathologic response. The primary endpoint is 2‑year overall survival (non-inferiority framing), with event-free survival assessed around 12 months after the first infusion. The key angle is “spare-adjuvant” de-escalation: today’s care for high-risk resectable stage III/limited stage IV melanoma commonly includes surgery plus prolonged adjuvant PD‑1 (or, for BRAF V600–mutant disease, adjuvant BRAF/MEK targeted therapy), and this trial tests whether an abbreviated pre-op immunotherapy-only approach can preserve survival while reducing treatment duration and toxicity burden.