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Phase 1, open-label, dose-escalation study on the safety, pharmacokinetics, and preliminary efficacy of intravenous Coxsackievirus A21 (V937), with or without pembrolizumab, in patients with advanced solid tumors.
Rudin, Charles M; Pandha, Hardev S; Zibelman, Matthew; Akerley, Wallace L; Harrington, Kevin J; Day, Daphne; Hill, Andrew G; O'Day, Steven J; Clay, Timothy D; Wright, Gavin M; Jennens, Ross R; Gerber, David E; Rosenberg, Jonathan E; Ralph, Christy; Campbell, David C; Curti, Brendan D; Merchan, Jaime R; Ren, Yixin; Schmidt, Emmett V; Guttman, Lisa; Gupta, Sumati.
Afiliación
  • Rudin CM; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA rudinc@mskcc.org.
  • Pandha HS; Professor of Medicine, Weill Cornell Medical College, New York, New York, USA.
  • Zibelman M; University of Surrey, Guildford, UK.
  • Akerley WL; Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA.
  • Harrington KJ; Division of Medical Oncology, Department of Internal Medicine, Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah, USA.
  • Day D; The Royal Marsden/The Institute of Cancer Research NIHR Biomedical Research Centre, London, UK.
  • Hill AG; Department of Oncology, Monash Health and Monash University, Clayton, Victoria, Australia.
  • O'Day SJ; Tasman Oncology Research Ltd, Southport, Queensland, Australia.
  • Clay TD; John Wayne Cancer Institute, Providence St John's Health Center, Santa Monica, California, USA.
  • Wright GM; Medical Oncology, St. John of God Subiaco Hospital, Perth, Western Australia, Australia.
  • Jennens RR; Department of Surgery, St Vincent's Hospital Melbourne, The University of Melbourne, Fitzroy, Australia; Division of Cancer Surgery, Peter MacCallum Cancer Centre, Parkville, Victoria, Australia.
  • Gerber DE; Epworth Healthcare, Richmond, Victoria, Australia.
  • Rosenberg JE; Division of Hematology-Oncology, Harold C. Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, Dallas, Texas, USA.
  • Ralph C; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
  • Campbell DC; Division of Medical Oncology, Institute of Oncology, St. James's University Hospital, Leeds, UK.
  • Curti BD; Western Health, Sunshine Hospital, St Albans, Victoria, Australia.
  • Merchan JR; Earle A. Chiles Research Institute at Robert W. Franz Cancer Center, Providence Cancer Institute, Portland, Oregon, USA.
  • Ren Y; University of Miami Miller School of Medicine/Sylvester Comprehensive Cancer Center, Miami, Florida, USA.
  • Schmidt EV; Merck & Co., Inc, Rahway, New Jersey, USA.
  • Guttman L; Merck & Co., Inc, Rahway, New Jersey, USA.
  • Gupta S; Practical Clinical, Mississauga, Ontario, Canada.
J Immunother Cancer ; 11(1)2023 01.
Article en En | MEDLINE | ID: mdl-36669791
BACKGROUND: Oncolytic virus V937 showed activity and safety with intratumoral administration. This phase 1 study evaluated intravenous V937±pembrolizumab in patients with advanced solid tumors. METHODS: Patients had advanced non-small cell lung cancer (NSCLC), urothelial cancer, metastatic castration-resistant prostate cancer, or melanoma in part A (V937 monotherapy), and metastatic NSCLC or urothelial cancer in part B (V937+pembrolizumab). Prior immunotherapy was permitted >28 days before study treatment. Patients received intravenous V937 on days 1, 3, and 5 (also on day 8 in part B) of the first 21-day cycle and on day 1 of subsequent cycles for eight cycles. Three ascending dose-escalation cohorts were studied. Dose-escalation proceeded if no dose-limiting toxicities (DLTs) occurred in cycle 1 of the previous cohort. In part B, patients also received pembrolizumab 200 mg every 3 weeks from day 8 for 2 years; dose-expansion occurred at the highest-dose cohort. Serial biopsies were performed. RESULTS: No DLTs occurred in parts A (n=18) or B (n=85). Grade 3-5 treatment-related adverse events (AEs) were not observed in part A and were experienced by 10 (12%) patients in part B. The most frequent treatment-related AEs (any grade) in part B were fatigue (36%), pruritus (18%), myalgia (14%), diarrhea (13%), pyrexia (13%), influenza-like illness (12%), and nausea (12%). At the highest tested dose, median intratumoral V937 concentrations were 117,631 copies/mL on day 8, cycle 1 in part A (n=6) and below the detection limit for most patients (86% (19/22)) on day 15, cycle 1 in part B. Objective response rates were 6% (part A), 9% in the NSCLC dose-expansion cohort (n=43), and 20% in the urothelial cancer dose-expansion cohort (n=35). CONCLUSIONS: Intravenous V937+pembrolizumab had a manageable safety profile. Although V937 was detected in tumor tissue, in NSCLC and urothelial cancer, efficacy was not greater than that observed in previous studies with pembrolizumab monotherapy. TRIAL REGISTRATION NUMBER: NCT02043665.
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Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Carcinoma de Pulmón de Células no Pequeñas / Virus Oncolíticos / Neoplasias Pulmonares Límite: Humans / Male Idioma: En Revista: J Immunother Cancer Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos

Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Carcinoma de Pulmón de Células no Pequeñas / Virus Oncolíticos / Neoplasias Pulmonares Límite: Humans / Male Idioma: En Revista: J Immunother Cancer Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos