Replimune’s oncolytic virus therapy RP1 (vusolimogene oderparepvec) won a favorable vote from the FDA’s Cellular, Tissue, and Gene Therapies Advisory Committee (CTGTAC) for an accelerated approval application in unresectable advanced cutaneous melanoma, with results deemed “evaluable and clinically meaningful.” The committee voted 10–3 after the FDA declined approval a second time in April, typically following advisory input even though it is not legally bound. The review centered on RP1 plus nivolumab (Opdivo) after PD-1 inhibitor progression, drawing attention to uncertainty around response-rate estimation. In the IGNYTE clinical study, an objective response rate (ORR) of 33.6% was reported in the phase 2 portion, but the FDA’s concerns included how RECIST evaluation handled injected target lesions—leading to an ORR that dropped to 15.7% when certain patients were excluded. Committee members described the decision as difficult due to response-rate and duration-of-response ambiguity. The advisory outcome sets up the next stage for regulator consideration as the FDA weighs the evidentiary package from a disease area with limited options after PD-1 failure.