News|Articles|July 29, 2026

FDA Advisory Committee to Weigh RP1 Plus Nivolumab in Anti–PD-1–Pretreated Advanced Melanoma

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Key Takeaways

FDA review progressed from a January 2025 priority BLA to two CRLs, driven largely by concerns that the single-arm, heterogeneous population limited attribution of RP1’s incremental benefit.
IGNYTE enrolled 140 post–anti–PD-1 advanced melanoma patients with measurable and injectable disease, using intratumoral RP1 q2w with staggered nivolumab initiation and extended maintenance dosing.
Blinded central review documented a 33.6% ORR with 15% complete responses and a median DOR of 33.7 months, suggesting clinically meaningful durability in a refractory population.
Safety was characterized by frequent but mostly low-grade TRAEs; grade 3/4 TRAEs occurred in 12.9% with no treatment-related deaths, and fatigue, chills, pyrexia, and nausea predominated.
In the post–PD-1 setting where approved options remain limited (notably TIL therapy), an off-the-shelf intratumoral/on-systemic regimen may offer broader practical accessibility for eligible patients.

The Cellular, Tissue, and Gene Therapies Advisory Committee will review Replimune’s twice-rejected BLA for RP1 plus nivolumab in advanced melanoma.

The FDA’s Cellular, Tissue, and Gene Therapies Advisory Committee (CTGTAC) will convene on July 30, 2026, to discuss and make recommendations on the biologics license application (BLA) seeking the approval of vusolimogene oderparepvec (RP1) in combination with nivolumab (Opdivo) for the treatment of adult patients with advanced melanoma who have previously received an anti–PD-1–containing regimen.¹

The open-session meeting follows the June 2026 submission of a third BLA seeking approval of the combination following 2 complete response letters (CRLs) from the regulatory agency.² The FDA assigned a review goal date of August 2, 2026. The BLA is supported by data from the phase 1/2 IGNYTE trial (NCT03767348).

RP1 is a herpes simplex virus type 1–based oncolytic immunotherapy engineered to express granulocyte-macrophage colony-stimulating factor and a fusogenic glycoprotein, and it is administered by intratumoral injection.³

“It’s important to point out that the [IGNYTE] trial design was done in collaboration and with advice from the [FDA], and [it] happened in a time when there was no real option in the patient population under study, which is basically those with advanced metastatic melanoma who have [progressed on] PD-1–containing therapy, including a combination of ipilimumab [Yervoy] and nivolumab,” Michael K. Wong, MD, PhD, FRCPC, said in an interview with OncLive®.

Wong is the former physician in chief and professor of oncology in the Department of Medicine at Roswell Park Comprehensive Cancer Center in Buffalo, New York, and was the lead study author on IGNYTE.

What is the regulatory history of RP1 plus nivolumab in advanced melanoma?

The FDA accepted the original BLA for RP1 plus nivolumab under priority review in January 2025, supported by breakthrough therapy designation and with a Prescription Drug User Fee Act target action date of July 22, 2025.⁴In the first CRL, the regulatory agency stated that the single-arm IGNYTE trial was not considered an adequate and well-controlled investigation capable of providing substantial evidence of effectiveness, in part because the heterogeneous trial population made it difficult to isolate the contribution of RP1.⁵

The company resubmitted the BLA, which was accepted in October 2025 with a target action date of April 10, 2026.⁶ The agency then issued a second CRL in April 2026, citing deficiencies related to both IGNYTE and the confirmatory phase 3 IGNYTE-3 trial (NCT06264180).⁷ The third BLA was accepted by the FDA as a class 1 response in June 2026, setting the August 2, 2026, goal date and scheduling the advisory committee meeting.²

How was the IGNYTE trial designed?

IGNYTE was a single-arm, multicohort study, and the registrational phase 2 melanoma cohort enrolled 140 patients with advanced disease that had progressed on a prior anti–PD-1–containing regimen.³ Eligibility required at least 8 weeks of anti–PD-1 therapy, alone or in combination with anti–CTLA-4 therapy, as the most recent prior treatment. Patients needed to have at least 1 measurable lesion per RECIST 1.1 criteria and injectable lesions comprising at least 1 cm in longest diameter.

RP1 Plus Nivolumab: What the CTGTAC Will Consider

The CTGTAC will discuss and make recommendations on a BLA for RP1 plus nivolumab in anti–PD-1–pretreated advanced melanoma; the FDA goal date is August 2, 2026.

The BLA relies on data from the single-arm phase 1/2 IGNYTE trial, which produced a BICR-assessed ORR of 33.6% (95% CI, 25.8%-42.0%).

The FDA has issued 2 prior CRLs for the regimen, citing the interpretability of the single-arm IGNYTE trial design and the contribution of RP1 vs nivolumab.

Patients received an initial intratumoral dose of RP1, followed by up to 7 additional doses every 2 weeks; nivolumab at 240 mg was initiated with the second RP1 dose and given every 2 weeks for up to 8 cycles, then continued at 480 mg every 4 weeks for up to an additional 21 cycles.

Overall response rate (ORR) per modified RECIST 1.1 criteria by blinded independent central review (BICR) served as the primary end point in the registration-intended cohort.

What efficacy and safety data were reported from IGNYTE?

RP1 plus nivolumab (n = 140) elicited an ORR of 33.6% (95% CI, 25.8%-42.0%) by BICR in the registrational cohort. The investigator-assessed ORR by RECIST 1.1 criteria was 32.9% (95% CI, 25.2%-41.3%), including a complete response rate of 15.0%. The median duration of response was 33.7 months (95% CI, 14.1-not reached).

Any-grade treatment-related adverse effects (TRAEs) occurred in 90.0% of patients, and 12.9% of patients experienced grade 3/4 TRAEs. No treatment-related deaths were reported.

The most common all-grade TRAEs reported in at least 20% of patients comprised fatigue (32.9%), chills (32.1%), pyrexia (30.7%), and nausea (22.1%).

“The only other FDA-approved therapy in [the post–PD-1 setting] presently is the use of tumor infiltrating lymphocytes [TILs].... I am a fan of using adoptive T-cell therapy and cellular therapy; I’ve done clinical trials in this area, and I’ve participated in many of the TIL trials. Knowing [which patients] may benefit from what [therapies] is important, but no matter how you look at it, it’s a little harder to get patients into TIL therapies,” Wong said. “In the treatment landscape, [RP1 plus nivolumab has] more of a universal appeal in this patient population.”

References

Cellular, Tissue, and Gene Therapies Advisory Committee. FDA. Updated July 29, 2026. Accessed July 29, 2026. https://www.fda.gov/advisory-committees/advisory-committee-calendar/cellular-tissue-and-gene-therapies-advisory-committee-july-30-2026-meeting-announcement-updated
Replimune announces FDA acceptance of RP1 biologics license application resubmission for advanced melanoma. News release. Replimune. June 26, 2026. Accessed July 29, 2026. https://ir.replimune.com/news-releases/news-release-details/replimune-announces-fda-acceptance-rp1-biologics-license
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
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 29, 2026. https://ir.replimune.com/news-releases/news-release-details/replimune-announces-biologics-license-application-acceptance-and
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 29, 2026. https://ir.replimune.com/news-releases/news-release-details/replimune-receives-complete-response-letter-fda-rp1-biologics
Replimune announces FDA acceptance of BLA resubmission of RP1 for the treatment of advanced melanoma. News release. Replimune. October 20, 2025. Accessed July 29, 2026. https://ir.replimune.com/news-releases/news-release-details/replimune-announces-fda-acceptance-bla-resubmission-rp1-0
Complete response letter for BLA 125827. FDA. Accessed July 29, 2026. https://download.open.fda.gov/crl/CRL_BLA125827_20260410.pdf