FDA Approves Vusolimogene Oderparepvec Plus Nivolumab for PD-1-Refractory Advanced Melanoma

Clinical Summary:

• Based on results from the phase 2 IGNYTE trial, the FDA has granted accelerated approval to vusolimogene oderparepvec plus nivolumab for patients with unresectable advanced cutaneous melanoma who experience disease progression following PD-1-blocking antibody-based treatment. 
• In this multicenter, single-arm study, the combination demonstrated durable objective responses in a heavily pretreated population, with a safety profile consistent with oncolytic viral therapy and immune checkpoint inhibition.
• The approval introduces the first oncolytic viral therapy combined with nivolumab for this indication and is contingent on confirmatory studies to verify clinical benefit under the FDA's accelerated approval pathway.

On August 6, 2026, the US Food and Drug Administration (FDA) granted accelerated approval to vusolimogene oderparepvec (Tudriqev; Replimune) plus nivolumab (Opdivo; Bristol Myers Squibb) for patients with advanced unresectable cutaneous melanoma who experience disease progression following PD-1-blocking antibody-based treatment. 

This approval was based on results from the phase 2 IGNYTE trial, an open-label, single-arm trial evaluating the intratumoral oncolytic viral therapy plus nivolumab in adult patients with stage IIIB, IIIC, or IV unresectable melanoma following prior anti-PD-1 therapy. Of the 140 enrolled patients, 91 patients with at least 1 noninjected lesion comprised the efficacy-evaluable population. 

Treatment with the combination produced an objective response rate (ORR) of 24.2% and a median duration of response of 14.1 months. The FDA granted approval under its accelerated approval pathway based on these efficacy findings. Continued approval will require verification of clinical benefit in postmarketing confirmatory trials.

The recommended dosage of vusolimogene oderparepvec is 1 mL/cm of the largest tumor dimension, up to a maximum of 10 mL across all injected lesions per treatment. The therapy is administered intratumorally once every 2 weeks for 8 consecutive doses, beginning at a concentration of 10⁶ plaque-forming units (PFU)/mL at week 1 and increasing to 10⁷ PFU/mL for subsequent doses. Nivolumab is initiated intravenously at week 3 according to its approved prescribing information.

The prescribing information includes warnings and precautions for accidental exposure, herpetic infection or reactivation, injection procedure complications, and immune-mediated adverse events. The most common adverse reactions include fatigue, pyrexia, infections, chills, musculoskeletal pain, nausea, diarrhea, injection-site reactions, headache, cough, influenza-like illness, rash, vomiting, pruritus, arthralgia, constipation, decreased appetite, dizziness, dyspnea, hemorrhage, edema, and abdominal pain.

Vusolimogene oderparepvec-wtpg plus nivolumab previously received FDA breakthrough therapy designation, and the agency reviewed the application through the accelerated approval pathway following a positive recommendation from the Cellular, Tissue, and Gene Therapies Advisory Committee.

Source:

US Food and Drug Administration. FDA grants accelerated approval to vusolimogene oderparepvec-wtpg in combination with nivolumab for melanoma. Accessed on August 6, 2026. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-vusolimogene-oderparepvec-wtpg-combination-nivolumab-melanoma