Replimune’s oncolytic melanoma therapy vusolimogene oderparepvec (RP1) cleared a key regulatory hurdle after the FDA’s Cellular, Tissue, and Gene Therapies Advisory Committee (CTGTAC) voted 10–3 that IGNYTE results were evaluable and clinically meaningful. The favorable recommendation comes after the FDA declined approval a second time in April. CTGTAC’s vote responded to Replimune’s accelerated approval application to use RP1 in combination with nivolumab (Opdivo) for adults with unresectable advanced cutaneous melanoma after progression on a PD-1 inhibitor. The committee noted that decision difficulty reflected uncertainty around response-rate magnitude and how to interpret the trial’s objective response rate. Replimune presented Phase 2 IGNYTE data showing an ORR of 33.6% (95% CI 25.8%–42.0%) and median duration of response of 24.8 months. However, FDA review concerns highlighted that 49% of patients had all target lesions injected, which RECIST 1.1 requires to be excluded from evaluation—reducing ORR to 15.7% when those patients were excluded. The vote keeps the program alive toward potential FDA action, while underscoring how trial conduct and response assessment rules remain central in oncolytic-virus submissions.