The FDA has granted accelerated approval to vusolimogene oderparepvec-wtpg (RP1; Tudriqev) in combination with nivolumab (Opdivo) for the treatment of adult patients with unresectable or metastatic melanoma who have progressed on a prior anti–PD-1–blocking regimen, according to a press release from the FDA.¹

The approval follows 2 complete response letters (CRLs), a third resubmission of the biologics license application (BLA), and a 10-3 favorable vote from the FDA’s Cellular, Tissue, and Gene Therapies Advisory Committee (CTGTAC) on July 30, 2026.²

Further, the press release from the FDA highlighted the accelerated approval designation was given because of the objective response rate and duration of response. Additionally, the drug’s developer must conduct post-approval trial(s) to verify the clinical benefit of RP1 plus nivolumab. Based on the results of the confirmatory trials(s) continued approval may be contingent.

The recommended dosage of RP1 is 1 mL/cm of the largest dimension of the tumor for a maximum of 10 mL across all treated lesions per dose. RP1 intratumoral injections should be given every 2 weeks for 8 consecutive doses, with a starting concentration of 10⁶ plaque-forming units (PFU) per mL at week 1, followed by 10⁷ PFU per mL for subsequent doses. Nivolumab should be given intravenously starting at week 3.

A Regulatory Path Marked by Setbacks

RP1 entered FDA review with momentum after earning breakthrough therapy designation in November 2024 and BLA acceptance with priority review in January 2025, which set an initial PDUFA date of July 22, 2025.^3,4 That cycle ended in a CRL on July 21, 2025, with the FDA concluding that the phase 1/2 IGNYTE trial (NCT03767348) did not qualify as an adequate and well-controlled study capable of supporting substantial evidence of effectiveness, citing heterogeneity within the trial population and unresolved questions about isolating RP1’s individual contribution within the combination regimen; no safety concerns were cited.⁵

The developer resubmitted the BLA in October 2025 with additional analyses, and the FDA accepted the resubmission under a Class II timeline, with a PDUFA date of April 10, 2026.⁶ A second CRL followed on April 10, 2026, with the FDA again finding the data insufficient to establish substantial evidence of effectiveness.⁷ The BLA was resubmitted and accepted by the FDA for a third time in June 2026, with the FDA acknowledging the decision as a complete, class I response and setting the PDUFA date for August 2, 2026. They also announced the July 30, 2026, CTGTAC meeting, which ultimately culminated in today’s approval.⁸

The Data Supporting Approval

The approval is supported by data from the IGNYTE trial, in which 140 patients with advanced melanoma who had confirmed disease progression on an anti–PD-1–based regimen received RP1 by intratumoral injection alongside intravenous nivolumab.⁹ By independent central review, the confirmed overall response rate (ORR) was 33.6% using modified RECIST v1.1 criteria and 32.9% by standard RECIST v1.1 criteria, with a median duration of response exceeding 35 months. Responses were observed in lesions that were not directly injected with RP1, a pattern investigators have pointed to as evidence of a systemic antitumor immune response.¹⁰

A 3-year landmark overall survival (OS) analysis presented at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting showed a median OS of 32.9 months, with 1-year, 2-year, and 3-year OS rates of 75.3%, 61.5%, and 47.8%, respectively. The median OS was not reached among responders, compared with 18.5 months among non-responders.¹¹

References

1. FDA grants accelerated approval to vusolimogene oderparepvec-wtpg in combination with nivolumab for melanoma. News release. FDA. August 6, 2026. Accessed August 6, 2026. https://tinyurl.com/49s5rvrc
2. Cellular, Tissue and Gene Therapies Advisory Committee (CTGTAC) Meeting. July 30, 2026. Accessed July 31, 2026. https://tinyurl.com/2n96zk7u
3. Replimune receives breakthrough therapy designation for RP1 and submits RP1 biologics license application to the FDA under the accelerated approval pathway. News Release. Replimune. November 21, 2024. Accessed July 24, 2026. https://tinyurl.com/2p8ym2tj
4. Replimune announces biologics license application acceptance and priority review for RP1 for the treatment of advanced melanoma. News release. Replimune. January 21, 2025. Accessed July 24, 2026. https://tinyurl.com/94jc39by
5. 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 July 24, 2026. https://tinyurl.com/2335n7sk
6. Replimune announces FDA acceptance of BLA resubmission of RP1 for the treatment of advanced melanoma. News release. Replimune. October 20, 2025. Accessed July 24, 2026. https://tinyurl.com/5yad7vza
7. Complete response. April 10, 2026. Accessed July 24, 2026. FDA. https://tinyurl.com/ys3etmrj
8. Replimune announces FDA acceptance of RP1 biologics license application resubmission for advanced melanoma. News release. June 26, 2026. Accessed July 24, 2026. https://tinyurl.com/4sdytzn4
9. Replimune announces positive topline primary analysis data by independent central review from IGNYTE clinical trial of RP1 plus nivolumab in anti-PD1 failed melanoma. News release. Replimune Group, Inc. June 6, 2024. Accessed July 24, 2026. https://tinyurl.com/mr3jxyh5
10. In GK, Wong MKK, Sacco JJ, et al. Response analysis for injected and non-injected lesions and of the safety and efficacy of superficial and deep/visceral RP1 injection in the registrational cohort of anti–PD-1–failed melanoma patients of the IGNYTE trial. J Clin Oncol. 2025;43(suppl 16):9537. doi:10.1200/JCO.2025.43.16_suppl.9537
11. Wong MKK, Sacco JJ, In GK, et al. A 3-year landmark overall survival analysis of RP1 plus nivolumab in patients with anti–PD-1–failed melanoma from the IGNYTE clinical trial. J Clin Oncol. 2026;44(suppl 16):9518. doi:10.1200/JCO.2026.44.16_suppl.9518