FDA Grants Priority Review to RP1 Plus Nivolumab for Advanced Melanoma After Anti–PD-1 Therapy

The FDA has accepted and granted priority review to the biologics license application (BLA) seeking the approval of RP1 (vusolimogene oderparepvec) in combination with nivolumab (Opdivo) for the treatment of adult patients with advanced melanoma who have received prior treatment with a PD-1 inhibitor–containing regimen.¹

The BLA has been assigned a target action date of July 22, 2025, under the Prescription Drug User Fee Act. The FDA does not anticipate holding an advisory committee meeting to discuss the application.

“There are limited treatment options and a significant unmet need for patients with advanced melanoma who previously received an anti–PD-1–containing regimen,” Sushil Patel, PhD, chief executive officer of Replimune, stated in a news release. “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.”

Data from the phase 1/2 IGNYTE trial (NCT03767348) supported the BLA. Findings presented at the 2024 SITC Annual Meeting showed that at a median follow-up of 15.4 months (range, 0.5-47.6) for patients treated in phase 2 of the study (n = 140), the confirmed overall response rate was 33.6% (95% CI, 25.8%-42.0%) per modified RECIST (mRECIST) 1.1 criteria by blinded independent central review (BICR) assessment; the complete response (CR) and partial response (PR) rates were 15.0% and 18.6%, respectively.²

Findings from a sensitivity analysis using RECIST 1.1 criteria showed the confirmed ORR was 32.9% (95% CI, 25.2%-41.3%). The respective CR and PR rates were 15.0% and 17.9%.

Notably, the combination previously received breakthrough therapy designation from the FDA for the same patient population in November 2024. This regulatory decision was supported by data from the anti-PD-1–progressed melanoma cohort of the IGNYTE trial. ³

The confirmatory phase 3 IGYNTE-3 trial (NCT06264180) has been initiated 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 has a planned enrollment at over 100 sites globally.¹

IGYNTE Overview and Safety Data

The phase 2 portion of the IGNYTE trial enrolled 140 patients with cutaneous melanoma who had progressed following prior anti–PD-1 therapy.² Eligibility criteria included at least 1 measurable and injectable lesion, adequate organ function, no prior oncolytic virus therapy, and an ECOG performance status of 0 or 1.

In cycle 1, beginning 28 days post-screening, patients received RP1 at a dose of 1 × 10⁶ pfu/mL. In cycles 2 through 8, patients received RP1 at a dose of 1 × 10⁷ pfu/mL plus 240 mg of nivolumab every 2 weeks. Nivolumab was continued at 240 mg in cycle 9, and it was then dosed at 480 mg every 4 weeks in cycles 10 through 30. Each treatment cycle lasted 2 weeks.

The study’s primary objective was to assess the safety and efficacy of RP1 plus nivolumab. Secondary end points 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.

Regarding safety, the combination (n = 156) primarily produced grade 1/2 adverse effects (AEs) with a low incidence of grade 3/4 AEs.⁴ The most common treatment-related AEs included chills (any-grade, 34.0%; grade 3, 0.7%), fatigue (33.3%; 1.3%), pyrexia (31.4%; 0%), nausea (22.4%; 0%), influenza-like illness (19.2%; 0%), injection site pain (14.7%; 0%), diarrhea (13.5%; 0.6%), vomiting (13.5%; 0%), headache (12.8%; 0%), pruritus (12.8%; 0%), asthenia (9.0%; 0.6%), arthralgia (7.1%; 0.7%), myalgia (7.1%; 0%), decreased appetite (6.4%; 0.6%), and rash (6.4%; 0.6%). The following grade 4 AEs were also observed in 1 patient each: increased alanine aminotransferase levels, increased blood bilirubin levels, cytokine release syndrome, hepatic cytosis, splenic rupture, and myocarditis. No grade 5 AEs were reported.

References

1. Replimune announces biologics license application acceptance and priority review for RP1 for the treatment of advanced melanoma.News release. Replimune. January 21, 2025. Accessed January 21, 2025. https://ir.replimune.com/news-releases/news-release-details/replimune-announces-biologics-license-application-acceptance-and
2. 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.
3. Replimune receives breakthrough therapy designation for RP1 and submits RO1 biologics license application to the FDA under the accelerated approval pathway. News release. Replimune Group. November 21, 2024. Accessed January 21, 2025. https://ir.replimune.com/news-releases/news-release-details/replimune-receives-breakthrough-therapy-designation-rp1-and
4. Wong MKK, Sacco JJ, Robert C, et al. Efficacy and safety of RP1 combined with nivolumab in patients with anti–PD-1–failed melanoma from the IGNYTE clinical trial. J Clin Oncol. 2024;42(suppl 16):9517. doi:10.1200/JCO.2024.42.16_suppl.9517