RP1 (VSV-GM-CSF) + Nivolumab Shrinks 97% of Injected and 97% of Bystander Lesions in PD-1–Refractory Melanoma

RP1, an oncolytic vaccine armed with GM-CSF and fusogenic GALV-GP-RCT, was injected Q2W into superficial and/or image-guided visceral tumors alongside nivolumab IV (240 mg Q2W) in 140 anti-PD-1–failed melanoma patients in the registrational IGNYTE cohort (NCT03767348). Independent review showed a 32.9% RECIST ORR with median DOR 33.7 mo. Among the 46 responders, 98.7% of 78 injected lesions and 96.6% of 119 non-injected lesions regressed, with ≥30% shrinkage in 93.5% and 79.0%, respectively; visceral bystander lesions shrank ≥30% in 65.4%. ORR was similar for superficial-only injections (29.8%) and for protocols including deep/visceral injections (41.7%). Grade ≥3 treatment-related AEs occurred in 14.4% (superficial) versus 8.3% (deep/visceral); pneumothorax was limited to 6% of lung injections, and no severe hepatic or bleeding events followed liver injections.