In an extraordinary move, 22 expert researchers behind the Phase III IGNYTE trial for Replimmune’s melanoma candidate RP1 publicly challenged the FDA’s complete response letter that led to the drug’s rejection. The FDA’s Oncology Center of Excellence chief Richard Pazdur intervened late in the review, overruling a favorable CDER and CBER consensus. Experts argue that the heterogeneous trial population reflects real-world diversity and that a monotherapy control arm would be impractical and unethical. This case highlights tensions in regulatory processes affecting cutting-edge immunotherapies.