RP1 Combined With Nivolumab in Advanced Anti-PD-1-Failed Melanoma (IGNYTE).

Publication date: Jul 08, 2025

Effective treatment options for melanoma after immune checkpoint blockade failure are limited. RP1 (vusolimogene oderparepvec) is an HSV-1-based oncolytic immunotherapy, here evaluated in combination with nivolumab in anti-PD-1-failed melanoma. Patients had advanced melanoma that had confirmed progression on anti-PD-1 (≥8 weeks, last prior treatment). RP1 was administered intratumorally (≤8 doses, ≤10 mL/dose; additional doses allowed) with nivolumab (≤2 years). The objective response rate (ORR) was assessed by independent central review using Response Evaluation Criteria in Solid Tumors version 1. 1. Of 140 patients enrolled, 48. 6% had stage IVM1b/c/d disease, 65. 7% had primary anti-PD-1 resistance, 56. 4% were PD-L1 negative, and 46. 4% received prior anti-PD-1 and anti-CTLA-4 therapy (43. 6% in combination and 2. 9% sequentially). Confirmed ORR (95% CI) was 32. 9% (25. 2%-41. 3%; 15. 0% complete response). Responses occurred with similar frequency, depth, duration, and kinetics for injected and non-injected, including visceral, lesions. Median (95% CI) duration of response was 33. 7 (14. 1-not reached) months. Overall survival rates (95% CI) at 1 and 2 years were 75. 3% (66. 9%-81. 9%) and 63. 3% (53. 6%-71. 5%), respectively. Biomarker analysis demonstrated broad immune activation associated with response, including increased CD8+ T-cell infiltration and PD-L1 expression. Treatment-related adverse event rates were 77. 1% grade 1/2, 9. 3% grade 3, 3. 6% grade 4, and no grade 5 events. RP1 combined with nivolumab provided deep and durable systemic responses in patients with anti-PD-1-failed melanoma, including those with poor prognostic factors. The safety profile was favorable, with mostly grade 1/2 adverse events. (Funded by Replimune, Inc. ; IGNYTE ClinicalTrials. gov, NCT03767348; EudraCT number, 2016-004548-12).

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