Krystal Biotech has suspended enrollment in its OPAL-1 Phase 1/2 trial evaluating intratumoral injections of KB707 for advanced skin cancer, citing heightened regulatory uncertainty after the U.S. Food and Drug Administration rejected a similar melanoma therapy from Replimune Group earlier this summer. Patients already dosed will continue to be followed, but no new participants will be added. The FDA issued a complete response letter to Replimune in June, saying data from a Phase 1/2 study of its herpes-based oncolytic immunotherapy RP1—showing a 32.9% objective response rate in 140 PD-1-refractory melanoma patients—did not constitute "substantial evidence of effectiveness" and criticized the trial’s heterogenous design. Krystal’s KB707 uses the same viral backbone and a comparable intratumoral delivery approach, prompting concern that accelerated-approval pathways for the class could be narrowing. Krystal will redirect resources to an inhaled formulation of KB707 that is being tested in the KYANITE-1 trial for non-small cell lung cancer. Interim data presented at ASCO showed a 36% objective response rate with no Grade 4 or 5 adverse events. The company has secured an End-of-Phase 2 meeting with the FDA in October to discuss potential registration paths for the inhaled therapy.