FDA Grants Type A Meeting to Discuss RP1 Plus Nivolumab in Advanced Melanoma

The FDA has scheduled a Type A meeting with Replimune Group, Inc. to discuss the complete response letter (CRL) that the FDA issued to Replimune’s biologics license application (BLA) seeking the approval of vusolimogene oderparepvec (RP1) plus nivolumab (Opdivo) for the treatment of patients with advanced melanoma who have previously been treated with a PD-1 inhibitor–containing regimen.^1,2

Notably, the FDA issued the CRL on July 22, 2025.² The CRL stated that the FDA did not consider the phase 1/2 IGNYTE trial (NCT03767348) to be a substantial and well-controlled clinical trial to provide adequate data to support the approval of the combination. The CRL also noted that the FDA could not adequately interpret the IGNYTE findings because of the heterogeneity of the enrolled patient population. Additionally, the CRL delineated action items for Replimune related to the design of the confirmatory trial. Notably, the CRL did not mention safety issues related to the study drugs.

According to a news release from Replimune, the company submitted a briefing book to the FDA that addressed the points cited in the CRL.¹ Points included prior agreements related to the patient population, criteria for determining PD-1 inhibitor resistance, the use of supporting literature, and comments about the design of the phase 3 confirmatory trial design. The book also features an additional analysis of data shared in the BLA.

“We are eager to engage in a productive discussion with the FDA to reach a swift resolution for the accelerated approval of RP1 in advanced melanoma,” Sushil Patel, PhD, chief executive officer of Replimune, stated in the news release. “The melanoma community, including leading physicians and patient advocacy groups, [has] emphasized the urgent need for access to RP1 based on the strength of the data and limited effective treatment options for this population. We remain steadfastly committed to patient access while we work with the FDA to secure regulatory approval for RP1; however, without accelerated approval based on the current application, continuation of the RP1 program in advanced melanoma, including the phase 3 confirmatory trial, will not be viable.”

Zooming in on the IGNYTE Trial

IGNYTE enrolled 140 patients with cutaneous melanoma that was refractory to PD-1 inhibition.³ Patients needed to have at least 1 measurable and injectable lesion, have had no prior exposure to oncolytic virus therapy, have adequate organ function, and have an ECOG performance status of 0 or 1.

In cycle 1, patients received RP1 at 1 × 10⁶ pfu/mL in cycle 1. In cycles 2 through 8, patients received RP1 at 1 × 10⁷ pfu/mL plus nivolumab at 240 mg every 2 weeks. Beginning in cycle 9 and continuing through cycle 30, patients received nivolumab monotherapy initially at 240 mg in cycle 9, and subsequently at 480 mg every 4 weeks.

Safety and overall response rate (ORR) served as the trial’s primary end points. Secondary end points included duration of response, complete response (CR) rate, disease control rate, progression-free survival, and the 1- and 2-year overall survival rates.

At a median follow-up of 15.4 months, the confirmed ORR (cORR) was 33.6% (95% CI, 25.8%-42.0%) per modified RECIST 1.1 criteria by blinded independent central review.³ The CR rate was 15.0%, and the partial response (PR) rate was 18.6%. Moreover, a sensitivity analysis using RECIST 1.1 criteria demonstrated that the combination elicited a cORR of 32.9% (95% CI, 25.2%-41.3%); the CR and PR rates were 15.0% and 17.9%, respectively.

References

1. Replimune announces Type A meeting scheduled with FDA. News release. Replimune Group, Inc. September 2, 2025. Accessed September 2, 2025. https://ir.replimune.com/news-releases/news-release-details/replimune-announces-type-meeting-scheduled-fda
2. Replimune receives complete response letter from FDA for RP1 biologics license application for the treatment of advanced melanoma. News release. Replimune. July 22, 2025. Accessed September 2, 2025. https://ir.replimune.com/news-releases/news-release-details/replimune-receives-complete-response-letter-fda-rp1-biologics
3. Wong M, Bommareddy PK, Middleton MR, et al. Primary analysis of the registration-intended cohort of patients with anti–PD-1–failed melanoma from the IGNYTE trial of RP1 plus nivolumab, including clinical subgroup and initial biomarker data. Presented at: 2024 SITC Annual Meeting; November 6-10, 2024; Houston, TX. Abstract 1504.