The FDA’s Cellular, Tissue, and Gene Therapies Advisory Committee (CTGTAC) backed Replimune’s oncolytic virus program for an accelerated-approval bid in unresectable advanced cutaneous melanoma. In a 10–3 vote, the panel found results from the IGNYTE study of vusolimogene oderparepvec (RP1) plus nivolumab “evaluable and clinically meaningful,” reversing course after the FDA declined approval in April. The recommendation targets adults whose disease progressed after a PD-1 inhibitor. The panel discussion highlighted major uncertainty around response rates because FDA concerns included trial conduct and lesion-evaluation alignment with RECIST 1.1, with injected target lesions accounting for nearly half of enrolled patients. Replimune’s submission used phase 2 single-group data showing an objective response rate (ORR) of 33.6% and median duration of response (DOR) of 24.8 months; after excluding patients with all target lesions injected, the ORR fell to 15.7% and median DOR to 14.1 months, underscoring the magnitude of interpretive gaps. While the FDA is not bound to follow advisory committee views, the panel’s vote is likely to influence the agency’s thinking as it weighs benefit in a setting with limited post–PD-1 options.