FDA staff reiterated concerns about Replimune’s RP1 investigational skin cancer therapy ahead of an advisory committee meeting. In briefing documents, the agency said the company’s third attempt at approval does not have adequate data to evaluate RP1’s efficacy itself, particularly when used in combination with Opdivo in patients previously treated with PD-1 inhibitors. The agency specifically challenged the reliance on a single-arm design and the ability of the study to determine whether RP1 locally injected therapy provides systemic benefit. Replimune countered in its own briefing materials that randomized trials adding a placebo to continued PD-1 blockade are “not feasible or ethical” given the lack of evidence for benefit from continued anti–PD-1 monotherapy in this population. The dispute centers on whether trial design elements can sufficiently isolate the treatment effect, a key question for regulators as they weigh approval pathways for contentious, locally administered oncology drugs.