FDA Grants Accelerated Approval to RP1 Plus Nivolumab in Advanced Melanoma

The FDA granted accelerated approval to RP1 (vusolimogene oderparepvec; Tudriqev), an oncolytic virus therapy, in combination with nivolumab (Opdivo), for the treatment of advanced melanoma following progression on an anti–PD-1–containing regimen.¹

The decision follows a July 30, 2026, meeting of the FDA’s Cellular, Tissue, and Gene Therapies Advisory Committee (CTGTAC), which voted 10-3 in favor of the potential accelerated approval based on data from the phase 2 IGNYTE trial (NCT03767348).² Despite the FDA raising concerns over the study design and clinical meaningfulness of the trial data, the committee supported the accelerated approval because of the unmet need in this setting, with the confirmatory IGNYTE-3 trial (NCT06264180) already underway to support regular approval.

“I think this will be a major opportunity for providers like myself and my colleagues to to offer hope and opportunities to treat patients with a serious disease condition, especially when it can be treatment refractory,” Vincent Ma, MD, a specialist in melanoma and skin cancers and associate professor at the University of Wisconsin School of Medicine and Public Health, said in an interview with Targeted Oncology.

Supporting Study Data

RP1 is an oncolytic herpes virus–derived therapy building on the potential of talimogene laherparepvec (T-VEC; Imlygic), the first FDA-approved oncolytic immunotherapy.³ The registrational phase 2 cohort of IGNYTE enrolled 140 patients with unresectable stage IIIB to IV cutaneous melanoma who received RP1 plus nivolumab after prior anti–PD-1 therapy. Patients received an initial intratumoral injection of RP1, with up to 7 additional doses every 2 weeks, alongside 240 mg of nivolumab every 2 weeks for up to 2 years.

The confirmed overall response rate (ORR) by independent central review was 33.6%, including a 15.0% complete response (CR) rate, with 69.5% of responses ongoing at 1 year. Median progression-free survival (PFS) was 3.6 months (95% CI, 2.0-5.0) across all patients, and an exploratory 3-year overall survival (OS) rate of 47.8% was reported.⁴ Notably, the ORR in noninjected lesions (28.7%) was comparable to that of injected lesions (31.5%), suggesting a systemic effect. The combination’s safety profile largely overlapped with that of nivolumab alone, without evidence of significant additive toxicity.³

Regulatory Path to Approval

RP1’s path to approval spanned nearly 2 years, with a complete response letter (CRL) issued in July 2025 over concerns that IGNYTE was not adequate and well controlled, questioning the heterogeneity of the enrolled population, and raising doubts about whether RP1’s individual contribution to the observed responses could be isolated from that of nivolumab.⁴ The FDA issued a second CRL in April 2026, reiterating many of the same concerns.

At the CTGTAC meeting, the FDA’s presenters argued that the study’s reported ORR and duration of response were difficult to interpret given the challenges of applying RECIST criteria to intratumoral therapy, and that a contribution-of-effect analysis for RP1 was not conclusively demonstrated. The committee voted in favor of the IGNYTE trial’s reliability based on the sizable magnitude of improvement seen, given that the patients were confirmed to be resistant to PD-1 therapy and not expected to respond to nivolumab alone.²

Clinical Need for New Approaches

The approval addresses a recognized gap in later-line treatment for patients with anti–PD-1–refractory melanoma, a population with limited options beyond lifileucel (Amtagvi), a tumor-infiltrating lymphocyte therapy that requires resource-intensive logistics and collaboration with surgery and cellular therapy specialists. The confirmatory phase 3 IGNYTE-3 trial, comparing RP1 plus nivolumab with physician’s choice of therapy in a similar patient population, remains ongoing, with primary completion expected in 2030 to verify the clinical benefit that supported this accelerated approval.^2,5

REFERENCES

1. FDA grants accelerated approval to vusolimogene oderparepvec-wtpg in combination with nivolumab for melanoma. FDA. August 6, 2026. Accessed August 6, 2026. https://tinyurl.com/34v89fmz

2. Meeting of the Cellular, Tissue, and Gene Therapies Advisory Committee. FDA. July 30, 2026. Accessed July 30, 2026. https://tinyurl.com/2yjnd7r3

3. 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

4. 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

4. 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 31, 2026. https://tinyurl.com/2x2zvr58

5. VO and nivolumab vs physician’s choice in advanced melanoma that progressed on anti-PD-1 & anti-CTLA-4 drugs (IGNYTE-3). ClinicalTrials.gov. NCT06264180. Updated February 9, 2026. Accessed July 31, 2026. https://clinicaltrials.gov/study/NCT06264180