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

Michael K Wong; Mohammed M 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 Lynn Bowles; Katy K Tsai; Céleste Lebbé; Caroline Gaudy-Marqueste; Mark R Middleton; Aglaia Skolariki; Adel Samson; Jason A Chesney; Ari M VanderWalde; Yousef Zakharia; Kevin J Harrington; Elizabeth Appleton; Praveen K Bommareddy; Junhong Zhu; Marcus Viana; Jeannie W Hou; Robert S Coffin; Caroline Robert

doi:10.1200/JCO-25-01346

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

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

Michael K Wong, Mohammed M Milhem, Joseph J Sacco, Judith Michels, Gino K In, Eva Muñoz Couselo, Dirk Schadendorf, Georgia M Beasley, Jiaxin Niu, Bartosz Chmielowski, …

Journal of clinical oncology, Vol.43(33), pp.3589-3599

11/20/2025

DOI: 10.1200/JCO-25-01346

PMCID: PMC12622257

PMID: 40627813

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Abstract

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).

Details

Title: Subtitle: RP1 Combined With Nivolumab in Advanced Anti-PD-1-Failed Melanoma (IGNYTE)
Creators: Michael K Wong - Roswell Park Comprehensive Cancer Center
Mohammed M Milhem - University of Iowa
Joseph J Sacco - Clatterbridge Cancer Centre NHS Foundation Trust
Judith Michels - Institut Gustave Roussy
Gino K In - University of Southern California
Eva Muñoz Couselo - Vall d'Hebron Institute of Oncology
Dirk Schadendorf - National Center for Tumor Diseases
Georgia M Beasley - Duke University
Jiaxin Niu - The University of Texas MD Anderson Cancer Center
Bartosz Chmielowski - University of California, Los Angeles
Trisha M Wise-Draper - University of Cincinnati
Tawnya Lynn Bowles - Intermountain Medical Center
Katy K Tsai - University of California, San Francisco
Céleste Lebbé - Université Paris Cité
Caroline Gaudy-Marqueste - Aix-Marseille Université
Mark R Middleton - University of Oxford
Aglaia Skolariki - Churchill Hospital
Adel Samson - University of Leeds
Jason A Chesney - University of Louisville
Ari M VanderWalde - West Cancer Center
Yousef Zakharia - University of Iowa
Kevin J Harrington - Institute of Cancer Research
Elizabeth Appleton - Institute of Cancer Research
Praveen K Bommareddy - Replimune, Inc., Woburn, MA, USA
Junhong Zhu - Replimune, Inc., Woburn, MA, USA
Marcus Viana - Replimune, Inc., Woburn, MA, USA
Jeannie W Hou - Replimune, Inc., Woburn, MA, USA
Robert S Coffin - Replimune, Inc., Woburn, MA, USA
Caroline Robert - Institut Gustave Roussy
Resource Type: Journal article
Publication Details: Journal of clinical oncology, Vol.43(33), pp.3589-3599
DOI: 10.1200/JCO-25-01346
PMID: 40627813
PMCID: PMC12622257
NLM abbreviation: J Clin Oncol
ISSN: 1527-7755
eISSN: 1527-7755
Publisher: American Society of Clinical Oncology
Grant note: Replimune, Inc. (Woburn, MA)
Supported by Replimune, Inc (Woburn, MA).
Language: English
Electronic publication date: 07/08/2025
Date published: 11/20/2025
Academic Unit: Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
Record Identifier: 9984847148302771

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