The FDA Accepts a BLA for RP1 Plus Opdivo in Advanced Melanoma

The FDA accepts a BLA for RP1 plus Opdivo in advanced melanoma.

The Food and Drug Administration (FDA) has accepted a Biologics License Application (BLA) with Priority Review for RP1 (vusolimogene oderparepvec) in combination with Opdivo (nivolumab) for patients with advanced melanoma, according to a press release from Replimune Group, Inc., a clinical stage biotechnology company.

Notably, the agency granted the Priority Review BLA a Prescription Drug User Fee Act (PDUFA) action date of July 22, 2025, which is the deadline set by the regulatory agency to review and approve the combination. The press release also noted that the FDA grants Priority Review to applications for medicines that may provide significant improvements in the safety or effectiveness of the treatment of a serious condition, if approved.

“There are limited treatment options and a significant unmet need for patients with advanced melanoma who previously received an anti-PD-1 containing regimen,” said Dr. Sushil Patel, Chief Executive Officer of Replimune, in the news release.

Furthermore, the FDA does not plan to hold an advisory committee meeting in relation to this application, and at this time have not identified any potential review issues, according to the release.

The BLA, which is supported by the primary analysis data from the IGNYTE trial, is evaluating RP1 combined with Opdivo in patients with anti-PD-1 failed melanoma. Additionally, the FDA previously granted Breakthrough Therapy designation to RP1 plus Opdivo for the treatment of patients with advanced melanoma, based on the safety and clinical activity observed in the anti-PD-1 failed melanoma cohort of the IGNYTE clinical trial.

A confirmatory, phase 3 IGNYTEE-3 trial is underway with over 100 sites planned globally. This trial will assess the combination in participants with advanced melanoma who have progressed on anti-PD-1 and anti-CTLA-4 therapies or are ineligible for anti-CTLA-4 treatment.

IGNYTE-3 is a randomized, controlled, multicenter, open-label clinical trial, according to the trial's information page on clinicaltrials.gov, which added that the investigation will compare the combination versus physician's choice treatment for patients with unresectable stage 3b to 4 cutaneous melanoma. These patients' disease will have progressed on an anti-PD-1 and an anti-CTLA-4 containing regimen — administered either as a combination regimen or in sequence — or these individuals are not candidates for treatment with an anti-CTLA-4 therapy.

With approximately 100,000 new cases and 8,000 deaths estimated in the United States in 2024, melanoma is currently the fifth most common cancer, for which standard of care therapy includes treatment with immune checkpoint blockade. However, approximately half of patients will not respond to or will progress after treatment. This creates a limited number of options following immune checkpoint blockade therapy and there remains no standard of care available to patients.

In order to address this gap in care, investigators are examining RP1, which is genetically armed with the fusogenic protein (GALV-GP R-) and GM-CSF. The agent is based on a proprietary strain of herpes simplex virus and is meant to maximize tumor killing potency, the immunogenicity of tumor cell death, and the activation of a systemic anti-tumor immune response.

The press release also noted that the RP1 agent is expected to be synergistic with most established and experimental cancer treatment modalities, lending to the agents' versatility to be developed alone or combined with a variety of other treatment options.

“The BLA acceptance is an important milestone for Replimune, and we look forward to working closely with the FDA on the review of our application,” Patel concluded in the press release.

For more news on cancer updates, research and education, don’t forget to subscribe to CURE®’s newsletters here.