Phase 2 fianlimab + cemiplimab tests dual LAG-3/PD-1 checkpoint blockade in resectable melanoma.

This Phase 2, open-label, randomized, parallel-assignment trial at UC Irvine evaluates perioperative “total neoadjuvant therapy” using fianlimab plus cemiplimab in patients with surgically resectable melanoma. Fianlimab (Regeneron/Sanofi) is a LAG-3 (CD223)–blocking monoclonal antibody intended to release an inhibitory brake on T-cell activation, while cemiplimab (Libtayo; Regeneron/Sanofi) is a PD-1 (CD279)–blocking monoclonal antibody to restore anti-tumor immune responses. Patients have macroscopic Stage IIIB–D cutaneous melanoma or oligometastatic resectable Stage IV (M1a–M1c), with exclusions including visceral/bone/brain metastases and certain melanoma subtypes (acral/ocular/mucosal). Participants are randomized to 3, 6, or 8 neoadjuvant doses every 3 weeks (fixed 1600 mg fianlimab + 350 mg cemiplimab), then surgery, then adjuvant dosing to complete a full perioperative course. The key angle is testing whether deeper pre-op immune priming (more neoadjuvant cycles) improves pathologic and longer-term outcomes versus shorter TNT; today’s care for resectable Stage III/selected Stage IV melanoma increasingly uses neoadjuvant PD-1–based immunotherapy plus surgery (and adjuvant therapy based on risk/response) rather than surgery alone.