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

作者：Michael K. Wong, Mohammed Milhem, Joseph J. Sacco, Judith Michels, Gino K. In, Eva Muñoz‐Couselo, Dirk Schadendorf, Georgia M. Beasley, Jiaxin Niu, Bartosz Chmielowski, Trisha M. Wise‐Draper, Tawnya L. Bowles, Katy K. Tsai, Célèste Lebbé, Caroline Gaudy‐Marqueste, Mark R. Middleton, Aglaia Skolariki, Adel Samson, Jason Chesney, Ari M. Vanderwalde, Yousef Zakharia, Kevin J. Harrington, Elizabeth Appleton, Praveen K. Bommareddy, Junhong Zhu, Marcus Vinícius Canário Viana, Jeannie W Hou, Robert S. Coffin, Caroline Robert · 发表于：Journal of Clinical Oncology · 年份：2025 · DOI：10.1200/jco-25-01346 · 被引用次数：40 · 研究领域：Virus-based gene therapy research、CAR-T cell therapy research、Immunotherapy and Immune Responses

PURPOSE Effective treatment options for melanoma after immune checkpoint blockade failure are limited. RP1 (vusolimogene oderparepvec) is a herpes simplex virus type 1–based oncolytic immunotherapy, here evaluated in combination with nivolumab in anti–PD-1–failed melanoma. METHODS 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. RESULTS 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–cytotoxic T-lymphocyte antigen-4 therapy (43.6% in combination and 2.9% sequentially). Confirmed ORR (95% CI) was 32.9% (95% CI, 25.2% to 41.3%; 15.0% complete response). Responses occurred with similar frequency, depth, duration, and kinetics for injected and noninjected, including visceral lesions. The median (95% CI) duration of response was 33.7 (95% CI, 14.1 to not reached) months. Overall survival rates (95% CI) at 1 and 2 years were 75.3% (95% CI, 66.9% to 81.9%) and 63.3% (95% CI, 53.6% to 71.5%), respectively. Biomarker analysis demonstrated broad immune activation associated with response, including increased CD8 + T-cell infiltration and PD-L1 expression. ...