FDA Approves RP1 Plus Nivolumab for Advanced Melanoma

The FDA has granted accerlated approved to Replimune Group’s vusolimogene oderparepvec-wtpg (RP1; Tudriqev) in combination with nivolumab for the treatment of adults with unresectable advanced melanoma who progressed on a prior anti-PD-1-containing regimen. The approval is based on objective response rate and duration of response data from the phase 1/2 IGNYTE trial (NCT03767348), with continued approval contingent on verification of clinical benefit in a confirmatory trial.¹ The approval follows Replimune's third biologics license application (BLA) submission for RP1.²

RP1’s approval caps a lengthy regulatory path, including 2 prior complete response letters (CRLs) issued on July 22, 2025, and April 10, 2026.^2-4 Replimune said the FDA assigned a new review team ahead of the second CRL and later signaled a more collaborative posture following changes in agency leadership.² RP1 carries breakthrough therapy designation and priority review, and the resubmission was classified by the FDA as a complete, class 1 response.^1,2

"With the approval of Tudriqev, we have a potent oncolytic immunotherapy that can be used in a broad population, including BRAF-naïve or pretreated, and adjuvant relapsed patients," said Michael K. Wong, MD, PhD, primary investigator of the IGNYTE study and former physician in chief and professor of oncology at Roswell Park Comprehensive Cancer Center in Buffalo, New York, in the news release. "Importantly, the therapy in combination with nivolumab drives immune activation with a favorable risk-benefit profile and can be injected into superficial and visceral lesions."¹

IGNYTE is an open-label, multicenter phase 1/2 study evaluating RP1 as monotherapy or combined with nivolumab in adults with advanced solid tumors, including a registrational melanoma cohort. The cohort enrolled 140 patients with confirmed disease progression on anti-PD-1-based therapy for at least 8 weeks, with or without anti-CTLA-4; 91 patients with at least one non-injected lesion made up the efficacy-evaluable population. In this population, RP1 plus nivolumab achieved an objective response rate of 24.2%, with a median duration of response of 14.1 months.

The efficacy-evaluable population included patients with stage 4 disease (80%), prior adjuvant anti-PD-1 treatment (13%), PD-L1-negative status (54%), lung lesions (45%), and liver lesions (24%).¹ RP1 is administered by direct intratumoral injection into superficial, deep, and visceral lesions, with imaging guidance used for deep or visceral tumors and dosing based on tumor size.

Replimune said analyses found no material difference in response rates between injected and non-injected lesions, addressing a key question around RP1's mechanism as an intralesional oncolytic virus.² The company noted the April 2026 CRL contradicted positions the FDA expressed during a September 2025 Type A meeting, including on the heterogeneity of the IGNYTE patient population.^2,3 The approval reflects the FDA's acceptance of RP1's contribution of effect evidence within the combination regimen.²

RP1 Safety Profile and Secondary Outcomes

RP1 combined with nivolumab was well tolerated, with mostly mild to moderate adverse events and no grade 4 or 5 common adverse events reported. The most common adverse reactions (incidence ≥10%) included nausea, diarrhea, vomiting, constipation, decreased appetite, abdominal pain, fatigue, pyrexia, chills, injection site reaction, influenza-like illness, infections, musculoskeletal pain, arthralgia, headache, dizziness, cough, dyspnea, rash, pruritus, and hemorrhage. Most treatment-related adverse reactions were grade 1 or 2 and transient.¹

Accelerated approval was granted based on ORR and duration of response, with continued approval contingent on verification of clinical benefit in a confirmatory trial. Replimune is running the phase 3 IGNYTE-3 trial (NCT06264180) to confirm RP1 plus nivolumab's clinical benefit. Eligible patients will have access to ReplimuneConnect Plus, a program supporting treatment access, reimbursement, and financial assistance.¹

Melanoma is the fifth most common cancer in the US, with roughly 105,000 new cases estimated in 2025 and nearly 8500 deaths annually. About half of patients do not respond to or progress after standard checkpoint blockade, and more than half who do respond progress within 6 months, facing a median overall survival of less than one year after progression.¹

Sam Guild, president of AIM at Melanoma, said the approval addresses a longstanding need in the melanoma community.

"Every year, more than 8,500 people die of melanoma in the U.S., and new treatment options are urgently needed," Guild said.

References

1. Replimune announces FDA accelerated approval of TUDRIQEV in combination with nivolumab for unresectable advanced cutaneous melanoma after progression on an anti-PD-1-based regimen. News release. Replimune Group. August 6, 2026. Accessed August 7, 2026. https://ir.replimune.com/news-releases/news-release-details/replimune-announces-fda-accelerated-approval-tudriqevtm
2. Replimune announces FDA acceptance of RP1 biologics license application resubmission for advanced melanoma. News release. Replimune Group. June 26, 2026. Accessed August 7, 2026. https://ir.replimune.com/news-releases/news-release-details/replimune-announces-fda-acceptance-rp1-biologics-license
3. Replimune receives complete response letter from the FDA for RP1 biologics license application for the treatment of advanced melanoma. News release. Replimune Group. April 10, 2026. Accessed August 7, 2026. https://ir.replimune.com/news-releases/news-release-details/replimune-receives-complete-response-letter-fda-rp1-biologics-0/
4. Replimune announces FDA acceptance of BLA resubmission of RP1 for the treatment of advanced melanoma. News release. Replimune Group. October 20, 2025. Accessed August 7, 2026. https://ir.replimune.com/news-releases/news-release-details/replimune-announces-fda-acceptance-bla-resubmission-rp1-0

Frequently Asked Questions

What is RP1 approved for?
RP1 (vusolimogene oderparepvec), in combination with nivolumab, has accelerated approval for adults with unresectable advanced cutaneous melanoma who progressed on an anti-PD-1 antibody-based regimen.

How does RP1 work?
RP1 is an oncolytic herpes simplex virus-based immunotherapy given by intralesional injection, designed to work alongside systemic anti-PD-1 blockade with nivolumab.

What did the IGNYTE trial show?
In the efficacy-evaluable population of 91 patients, RP-1 plus nivolumab achieved a 24.2% objective response rate with a median duration of response of 14.1 months.