Oncolytic HSV‑1 RP1 plus PD‑1 blockade yields 33% ORR in PD‑1‑refractory melanoma

Vusolimogene oderparepvec (RP1) is an intratumoral HSV‑1 oncolytic virus engineered to secrete GM‑CSF and drive syncytia formation; in the single‑arm Phase II IGNYTE cohort (NCT03767348) it was paired with nivolumab for up to 2 years in 140 patients whose melanoma had progressed on prior anti‑PD‑1 (46% also exposed to anti‑CTLA‑4). Independent review showed a 32.9% ORR (15% CR), median DoR 33.7 mo, and 1‑/2‑yr OS rates of 75%/63%. Grade 3/4 treatment‑related AEs were 13%, notably lower than the ~57% grade 3/4 burden and comparable 28–31% ORR of salvage ipilimumab + nivolumab, and well above the ~9% ORR of ipilimumab alone.