The FDA’s recent complete response letter to Replimune’s RP1 oncolytic virus therapy marks a pivotal regulatory setback, signaling a stricter era for oncology drug approvals. RP1, engineered with dual genetic modifications for direct tumor destruction and immune activation, showed promise with a 32.9% overall response rate in PD-1 refractory melanoma during the IGNYTE trial. Despite surpassing prior benchmarks set by other oncolytic therapies, the $900 million program faced a dramatic market reaction with a 75% stock plunge. This regulatory decision reflects a growing emphasis on methodological rigor over accelerated approval pathways in cancer therapeutics.