Resubmission of a biologics license application (BLA) seeking the approval of vusolimogene oderparepvec (RP1) in combination with nivolumab (Opdivo) for patients with advanced melanoma is planned following productive communications with the FDA, according to a news release from the drug’s developer, Replimune.¹
The FDA has indicated it will treat the resubmission as an urgent matter upon receipt and will prioritize its review, citing the significant unmet need among patients with advanced melanoma who have progressed on prior PD-1–based therapy.
“We are grateful to the FDA leadership for their willingness to engage in a collaborative dialogue toward finding a meaningful path forward for RP1,” Sushil Patel, PhD, chief executive officer of Replimune, stated in the news release. “We are encouraged by the agency’s commitment to supporting patients and [United States] innovation, and look forward to working closely with the FDA to bring this important therapy to the advanced melanoma community as swiftly as possible.”
RP1 BLA Heads Back to the FDA for Review
- Replimune has announced plans to resubmit the BLA for vusolimogene oderparepvec (RP1) plus nivolumab in advanced melanoma after the FDA agreed to prioritize review of the resubmission as an urgent matter.
- This resubmission announcement follows 2 earlier CRLs issued by the FDA for the RP1 BLA in July 2025 and April 2026.
- The submission is supported by data from the IGNYTE trial; its review will be prioritized by the FDA due to the significant unmet need for effective treatment options for patients with advanced melanoma who have progressed on prior PD-1–based therapy.
What is the regulatory history of RP1 plus nivolumab in melanoma?
This resubmission announcement follows 2 earlier FDA review cycles, in which the agency issued a complete response letter (CRL) for each of the 2 prior RP1 BLAs.
The first CRL, issued in July 2025, cited issues with the design of the single-arm phase 2 IGNYTE trial (NCT03767348), leading to a dearth of evidence substantial enough for approval.2 Items to be addressed regarding the trial’s design, according to the CRL, included the need to demonstrate the isolated contribution of RP1 to the overall efficacy profile of the combination.
Based on this feedback, Replimune requested a Type A meeting with the FDA, during which a potential path toward the regimen’s accelerated approval was discussed.3
Following the Type A meeting, Replimune resubmitted the BLA with additional trial data, study information, and analyses, which the FDA accepted for review.4 However, in April 2026, the FDA issued a second CRL, citing deficiencies related to both IGNYTE and the phase 3 IGNYTE-3 trial (NCT06264180), which is comparing RP1 and nivolumab with treatment of physician’s choice in patients with advanced melanoma who progressed on PD-1– and CTLA-4–directed agents.5 In the second CRL, the agency asserted that the clinical evidence presented in both studies did not meet the regulatory approval standards.
What data supported these BLA submissions?
Data from the IGNYTE trial supported the original BLA submission and will form the basis of the resubmission package.1,2 IGNYTE was a single-arm study evaluating RP1 plus nivolumab in patients with unresectable stage IIIB to IV cutaneous melanoma whose disease progressed following at least 8 weeks of prior anti–PD-1 therapy.6
Results from IGNYTE were previously published in the Journal of Clinical Oncology. Evaluable patients with advanced melanoma who experienced confirmed progression on prior anti–PD-1 therapy (n = 140) achieved an objective response rate of 32.9% (95% CI, 25.2%-41.3%), which comprised a complete response rate of 15.0% (95% CI, 9.5%-22.0%). The median duration of response was 33.7 months (95% CI, 14.1-not reached). Moreover, the 1- and 2-year overall survival rates were 73.5% (95% CI, 66.9%-81.9%) and 63.3% (95% CI, 53.6%-71.5%), respectively.
The safety profile of RP1 plus nivolumab was consistent with the established profiles of oncolytic therapies and immune checkpoint inhibitors. Treatment-related adverse effects (TRAEs) of any grade were reported in 90.0% of patients, and 12.9% experienced grade 3 or 4 TRAEs. The most frequently reported TRAEs of any grade were fatigue (32.9%), chills (32.1%), pyrexia (30.7%), and nausea (22.1%). Grade 4 TRAEs occurred in 3.6% of patients and included cytokine release syndrome, hepatic cytolysis, elevated lipase levels, myocarditis, and splenic rupture. No treatment-related deaths were reported.
References
- Replimune announces planned RP1 BLA resubmission following productive discussion with FDA. News release. Replimune. May 29, 2026. Accessed May 29, 2026. https://ir.replimune.com/news-releases/news-release-details/replimune-announces-planned-rp1-bla-resubmission-following
- 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 May 29, 2026. https://ir.replimune.com/news-releases/news-release-details/replimune-receives-complete-response-letter-fda-rp1-biologics
- Replimune provides update following Type A meeting with FDA. News release. Replimune. September 18, 2025. Accessed May 29, 2026. https://ir.replimune.com/news-releases/news-release-details/replimune-provides-update-following-type-meeting-fda
- Replimune announces FDA acceptance of BLA resubmission of RP1 for the treatment of advanced melanoma. News release. Replimune. October 20, 2025. Accessed May 29, 2026. https://ir.replimune.com/news-releases/news-release-details/replimune-announces-fda-acceptance-bla-resubmission-rp1-0Complete response letter for BLA 125827. FDA. Accessed May 29, 2026. https://download.open.fda.gov/crl/CRL_BLA125827_20260410.pdf
- Complete response letter for BLA 125827. FDA. Accessed May 29, 2026. https://download.open.fda.gov/crl/CRL_BLA125827_20260410.pdf
- Wong MK, Milhem MM, Sacco JJ, et al. RP1 combined with nivolumab in advanced anti-PD-1-failed melanoma (IGNYTE). J Clin Oncol. 2025;43(33):3589-3599. doi:10.1200/JCO-25-01346
