Oncolytic HSV RP1 + PD-1 blockade nets 33% ORR and mDOR of 33.7 months, systemic lesion shrinkage in refractory melanoma

Vusolimogene oderparepvec (RP1) is a GM-CSF/fusogenic glycoprotein-armed oncolytic HSV-1 that was injected into tumors alongside nivolumab in the single-arm Phase II IGNYTE registrational cohort (NCT03767348). Among 140 anti-PD-1–refractory melanoma patients, investigator-reviewed ORR was 32.9% with a median DOR of 33.7 months. Of 197 measured lesions in 46 responding patients, partial response (shrinkage greater than 30%) was seen in 93.5% of injected and 79.0% of non-injected lesions, including 65.4% of non-injected visceral lesions, and thus evidence of a abscopal effect. Patients with superficial injections had an ORR of 29.8%, whereas those with deep/visceral +/- superficial had an ORR of 41.7%. Grade ≥3 TRAEs ran 14% (superficial) vs 8% (deep/visceral) and pneumothorax was 5.8% of lung injections—lower toxicity than salvage ipilimumab + nivolumab (ORR 14-22%, grade ≥3 ≈40-55%) and comparable efficacy to surface-only T-VEC + pembrolizumab (ORR ~40-47%).