Replimune Group’s RP1 plus nivolumab revived momentum after an FDA advisory committee supported the therapy for anti–PD-1-refractory advanced melanoma, despite negative briefing documents. The company’s BLA for RP1 in combination was submitted in November 2024 and relied on its single-arm IGNYTE Phase I/II registrational cohort, alongside designations including breakthrough therapy status and priority review. The outcome highlights the volatility that can accompany single-arm immuno-oncology programs as regulators weigh benefit-risk in difficult-to-treat settings. For investors, it extends the risk-reward profile of RP1 at a time when melanoma is highly competitive and checkpoint resistance remains a major clinical challenge. Replimune’s roller-coaster trajectory—supported by prior designations and clinical cohort data—may now translate into stronger commercial expectations if the FDA’s final decision aligns with the panel’s direction.