The FDA has accepted and granted priority review to Replimune's Biologics License Application (BLA) for vusolimogene oderparepvec (RP1) in combination with nivolumab (Opdivo) for the treatment of patients with advanced melanoma who have previously progressed on anti-PD-1 therapy. The FDA has set a Prescription Drug User Fee Act (PDUFA) action date of July 22, 2025.
The BLA is supported by data from the Phase 1/2 IGNYTE trial, which evaluated the safety and efficacy of RP1 in combination with nivolumab in patients with advanced melanoma who had progressed on prior anti-PD-1 therapy. Findings presented at the 2024 SITC Annual Meeting showed a confirmed overall response rate (ORR) of 33.6% (95% CI, 25.8%-42.0%) per modified RECIST (mRECIST) 1.1 criteria by blinded independent central review (BICR) assessment, with complete response (CR) and partial response (PR) rates of 15.0% and 18.6%, respectively.
IGNYTE Trial Details
The Phase 2 portion of the IGNYTE trial enrolled 140 patients with cutaneous melanoma who had progressed following prior anti-PD-1 therapy. Patients received RP1 at a dose of 1 × 10^6 pfu/mL in cycle 1, followed by 1 × 10^7 pfu/mL in cycles 2-8, along with 240 mg of nivolumab every 2 weeks. Nivolumab was continued at 240 mg in cycle 9 and then dosed at 480 mg every 4 weeks in cycles 10-30.
The primary objective of the study was to assess the safety and efficacy of RP1 plus nivolumab. Secondary endpoints included ORR, duration of response (DOR), CR rate, disease control rate, progression-free survival, 1-year overall survival (OS) rate, and 2-year OS rate.
Safety Profile
The combination of RP1 and nivolumab demonstrated a manageable safety profile, with primarily grade 1/2 adverse effects (AEs) and a low incidence of grade 3/4 AEs. The most common treatment-related AEs included chills (34.0%), fatigue (33.3%), and pyrexia (31.4%).
Ongoing Phase 3 Trial
A confirmatory Phase 3 trial, IGNYTE-3 (NCT06264180), is currently underway to assess RP1 plus nivolumab in patients with advanced melanoma who have progressed on anti-PD-1 and anti-CTLA-4 therapies or are ineligible for treatment with an anti-CTLA-4 agent. The study plans to enroll over 100 sites globally.
About RP1
RP1 (vusolimogene oderparepvec) is Replimune’s lead product candidate and is based on a proprietary strain of herpes simplex virus engineered and genetically armed with a fusogenic protein (GALV-GP R-) and GM-CSF. It is designed to maximize tumor killing potency, the immunogenicity of tumor cell death, and the activation of a systemic anti-tumor immune response.
Unmet Need in Advanced Melanoma
Melanoma is the fifth most common cancer, with approximately 100,000 new cases and 8,000 deaths estimated in the U.S. in 2024. Approximately half of patients treated with immune checkpoint blockade, the current standard of care therapy, do not respond or progress after treatment. There are limited treatment options and a significant unmet need for patients with advanced melanoma who previously received an anti-PD-1 containing regimen.
