FDA staff reiterated concerns that Replimune’s investigational melanoma therapy RP-1 lacks adequate evidence of efficacy ahead of a Cellular, Tissue and Gene Therapies advisory committee meeting. In briefing documents ahead of the July 30 discussion, the agency flagged the single-arm Ignyte Phase II design as insufficient to determine whether RP-1 meaningfully benefits patients and whether any systemic effects can be supported by the data when RP-1 is administered locally. Replimune countered that randomized controls on top of PD-1 inhibitors would be infeasible or unethical in the post–PD-1 setting, but the FDA’s internal analysis reportedly diverged from the company’s statistical results. The dispute centers on the objective response rate and duration of response used to support the proposed benefit. The case adds another layer to the growing regulatory pressure on single-arm oncology datasets and could shape what evidence types sponsors will be expected to generate for difficult-to-design local immunotherapies.