RP1 Combined With Nivolumab in Advanced Anti–PD-1–Failed Melanoma (IGNYTE)
Abstract
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. Treatment-related adverse event rates were 77.1% grade 1/2, 9.3% grade 3, 3.6% grade 4, and no grade 5 events. CONCLUSION 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.
Article Details
Journal Info
Journal of Clinical Oncology
Lippincott Williams & Wilkins
Authors (29)
Michael K. Wong
Mohammed M. Milhem
Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA
Joseph J. Sacco
Judith Michels
Département de Médecine Oncologique, Gustave Roussy, Villejuif, France
Gino K. In
Eva Muñoz Couselo
Vall d’Hebron Institute of Oncology (VHIO) and Vall d’Hebron Hospital Medical Oncology Department, Barcelona, Spain
Dirk Schadendorf
Georgia M. Beasley
Duke Cancer Institute, Duke University, Durham, NC
Jiaxin Niu
Banner MD Anderson Cancer Center, Gilbert, AZ
Bartosz Chmielowski
Trisha M. Wise-Draper
Tawnya Lynn Bowles
Intermountain Medical Center, Murray, UT
Katy K. Tsai
Céleste Lebbé
Caroline Gaudy-Marqueste
From the Sandra and Edward Meyer Cancer Center (J.D.W.) and the Department of Medicine (J.D.W., M.A.P.), Weill Cornell Medicine, and Memorial Sloan Kettering Cancer Center (M.A.P.) — both in New York; Istituto Oncologico Veneto, IRCCS, Padua (V.C.-S.), European Institute of Oncology, IRCCS, Milan (P.Q.), Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori, IRCCS, Meldola (M.G.), University of Siena and the Center for Immuno-Oncology, University Hospital of Siena, Siena (M.M.), and Istituto Nazionale Tumori IRCCS Fondazione Pascale, Naples (P.A.A.) — all in Italy; Maria Sklodowska-Curie National Institute of Oncology, Warsaw, Poland (P.R.); Texas Oncology–Baylor Charles A. Sammons Cancer Center, Dallas (C.L.C.); University Hospital Essen, the German Cancer Consortium, the National Center for Tumor Diseases–West, the Research Alliance Ruhr, Research Center One Health, and University Duisburg-Essen — all in Essen, Germany (D.S.); the College of Medicine, Swansea University, Swansea (J.W.), Brist...
Mark R. Middleton
Aglaia Skolariki
Churchill Hospital and University of Oxford, Oxford, United Kingdom
Adel Samson
Leeds Institute of Medical Research at St. James’s, University of Leeds, Leeds, United Kingdom
Jason A. Chesney
James Graham Brown Cancer Center, University of Louisville, Louisville, KY
Ari M. VanderWalde
West Cancer Center and Research Institute, Germantown, TN
Yousef Zakharia
Division of Hematology and Medical Oncology, Department of Internal Medicine Mayo Clinic Phoenix Arizona USA
Kevin J. Harrington
Institute of Cancer Research, Royal Marsden Hospital, London
Elizabeth Appleton
Praveen K. Bommareddy
Replimune, Inc, Woburn, MA
Junhong Zhu
Replimune, Inc, Woburn, MA
Marcus Viana
Replimune, Inc., Woburn, MA
Jeannie W. Hou
Replimune, Inc, Woburn, MA
Robert S. Coffin
Replimune, Inc, Woburn, MA
Caroline Robert