FDA Approves RP1 Plus Nivolumab for Advanced Melanoma

The FDA has granted accerlated approved to Replimune Group’s vusolimogene oderparepvec (RP1; TUDRIQEV) in combination with nivolumab for the treatment of adults with advanced melanoma who progressed on a prior anti-PD-1-containing regimen.¹ The approval follows Replimune's third biologics license application (BLA) submission for RP1, based on efficacy and safety data from the phase 2 IGNYTE trial (NCT03767348).²

The approval caps a lengthy regulatory path for RP1, 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

“This is a transformative moment for Replimune, marking years of pioneering research to bring TUDRIQEV to patients desperately in need of new treatment options for advanced melanoma,” said Sushil Patel, PhD, CEO of Replimune, in the news release. “We are deeply grateful to the melanoma community, including patients and investigators who participated in the clinical trial, for their tremendous support of this approval. We also would like to thank the FDA for recognizing the urgency to get this therapy to patients. Replimune is now focused on critical activities to deliver TUDRIQEV to as many patients as possible.”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

Among responding patients, median progression-free survival was 30.6 months with RP1 plus nivolumab, compared with 4.4 months on patients' prior anti-PD-1-based regimen. Replimune characterized RP1's safety profile in IGNYTE as favorable, though the company's disclosures do not specify adverse event rates. No new safety signals were reported by the company in connection with the approval.²

A global phase 3 confirmatory trial, IGNYTE-3, is underway to satisfy the FDA's accelerated approval requirements for RP1.² Approximately half of patients with advanced melanoma do not respond to or progress after standard immune checkpoint blockade, a population now eligible for RP1 as a second-line option.² Replimune received priority review for the RP1 application in recognition of this unmet need.^1,2

"We are pleased the FDA has demonstrated urgency in reconsidering the RP1 BLA with an expeditious action date in recognition of the significant unmet need for advanced melanoma patients and support from the broader melanoma community," said Sushil Patel, PhD, CEO of Replimune, in a previous news release. "We look forward to a productive scientific and clinical discussion on the risk/benefit profile of RP1 in this difficult to treat setting."2

RP1's approval adds a second-line option for patients with advanced melanoma who progress on checkpoint inhibitor therapy, an area with limited approved alternatives.² Replimune's ongoing IGNYTE-3 trial (NCT06264180) will determine whether the accelerated approval converts to full approval based on confirmatory results.²

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 June 26, 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 June 26, 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 June 26, 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, is approved for adults with advanced melanoma who progressed on a prior anti-PD-1-containing 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?
IGNYTE showed a 34% objective response rate with a median duration of response of 24.8 months in patients treated with RP1 plus nivolumab.