Academic Journal
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.
| Τίτλος: | 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. |
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| Συγγραφείς: | Rudin CM; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA rudinc@mskcc.org.; Professor of Medicine, Weill Cornell Medical College, New York, New York, USA., Pandha HS; University of Surrey, Guildford, UK., Zibelman M; Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA., Akerley WL; Division of Medical Oncology, Department of Internal Medicine, Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah, USA., Harrington KJ; The Royal Marsden/The Institute of Cancer Research NIHR Biomedical Research Centre, London, UK., Day D; Department of Oncology, Monash Health and Monash University, Clayton, Victoria, Australia., Hill AG; Tasman Oncology Research Ltd, Southport, Queensland, Australia., O'Day SJ; John Wayne Cancer Institute, Providence St John's Health Center, Santa Monica, California, USA., Clay TD; Medical Oncology, St. John of God Subiaco Hospital, Perth, Western Australia, Australia., Wright GM; 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., Jennens RR; Epworth Healthcare, Richmond, Victoria, Australia., Gerber DE; Division of Hematology-Oncology, Harold C. Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, Dallas, Texas, USA., Rosenberg JE; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA., Ralph C; Division of Medical Oncology, Institute of Oncology, St. James's University Hospital, Leeds, UK., Campbell DC; Western Health, Sunshine Hospital, St Albans, Victoria, Australia., Curti BD; Earle A. Chiles Research Institute at Robert W. Franz Cancer Center, Providence Cancer Institute, Portland, Oregon, USA., Merchan JR; University of Miami Miller School of Medicine/Sylvester Comprehensive Cancer Center, Miami, Florida, USA., Ren Y; Merck & Co., Inc, Rahway, New Jersey, USA., Schmidt EV; Merck & Co., Inc, Rahway, New Jersey, USA., Guttman L; Practical Clinical, Mississauga, Ontario, Canada., Gupta S; Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah, USA. |
| Πηγή: | Journal for immunotherapy of cancer [J Immunother Cancer] 2023 Jan; Vol. 11 (1). |
| Τύπος έκδοσης: | Clinical Trial, Phase I; Journal Article; Research Support, N.I.H., Extramural |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: BMJ Publishing Group Ltd Country of Publication: England NLM ID: 101620585 Publication Model: Print Cited Medium: Internet ISSN: 2051-1426 (Electronic) Linking ISSN: 20511426 NLM ISO Abbreviation: J Immunother Cancer Subsets: MEDLINE |
| Imprint Name(s): | Publication: 2020- : London, United Kingdom : BMJ Publishing Group Ltd. Original Publication: London : BioMed Central, 2013- |
| Ιατρικοί όροι (MeSH): | Carcinoma, Non-Small-Cell Lung*/drug therapy , Lung Neoplasms*/drug therapy , Oncolytic Viruses*, Antibodies, Monoclonal, Humanized/adverse effects ; Male ; Humans |
| Περίληψη: | 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. (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.) |
| Competing Interests: | Competing interests: CMR has consulted regarding oncology drug development with AbbVie, Amgen, AstraZeneca, Epizyme, Genentech/Roche, Ipsen, Jazz, Lilly, and Syros. He serves on the scientific advisory boards of Bridge Medicines, Earli, and Harpoon Therapeutics. HSP has received speaker and advisory board honoraria from Ipsen, Eisai, Pfizer, and Bristol Myers Squibb. MZ has received research support (to institution) from Bristol Myers Squibb and Exelixis. He has received advisory board honoraria from Aveo, Exelixis, Janssen, Pfizer, and EMD Serono. WLA is a data safety monitoring board member for Lilly. KJH has received research funding from AstraZeneca, Boehringer-Ingelheim, MSD, and Replimune. He serves on the scientific advisory boards of Arch Oncology, AstraZeneca, Bristol Myers Squibb, Boehringer-Ingelheim, Codiak BioSciences, Inzen Therapeutics, ISA Pharma, Merck-Serono, MSD, Pfizer, and Replimune. He serves on the speaker’s bureau for Bristol Myers Squibb, MSD, and Replimune. DD has received research support (to institution) from Ambrx Biopharma, Beigene, Bristol Myers Squibb, EpimAb, Harbour BioMed, Maxinovel, MSD, Olema Pharmaceuticals, Pfizer, PhamAbcine, Roche, and Haihe Biopharma. She serves on the scientific advisory board of MSD and has received travel support from Novartis. AGH has nothing to disclose. SJO has served on the scientific advisory boards of Biontech, Ultimovacs, Merck, ImaginAB, and Array. He was a consultant for Rad Immune, Bristol Myers Squibb, and Biontech; has served on the speaker’s board for Bristol Myers Squibb; and has received honoraria from Array, Ultimovacs, Merck, Rad Immune, ImaginAB, Biontech, and Bristol Myers Squibb. TDC has received honoraria from AstraZeneca, Merck USA, Novartis, Roche, and Specialized Therapeutics Australia; travel/accommodation support from Astellas; conference support from Novartis; and research support (to institution) from Daiichi Sankyo, Beigene, Janssen, Amgen, Exelixis, Merck, Immutep, and Clovis. He serves on the scientific advisory boards of AstraZeneca, Novartis, and Cipla. GMW has received speaker honoraria from AstraZeneca, Medtronic, Johnson & Johnson, and Device Technologies Australia and consulting fees (Expert Input Forum) from MSD. RRJ has nothing to disclose. DEG has received research funding from AstraZeneca, BerGenBio, and Karyopharm. He serves on the scientific advisory boards of Regeneron, Sanofi, Jansen, Mirati, and Catalyst and on the steering committee of Bristol Myers Squibb. He is a shareholder in Gilead. JER has received research funding (institutional) from Bayer, SeaGen, AstraZeneca, Roche/Genentech, Astellas, and QED Therapeutics. He has received consulting fees from IMVax, Century Tx, Aadi, Alligator, Hengrui, Bayer, SeaGen, AstraZeneca, Roche/Genentech, Astellas, QED Therapeutics, Bristol Myers Squibb, Merck, Pfizer, Pharmacyclics, Boehringer Ingelheim, GlaxoSmithKline, Infinity, Janssen, Mirati, EMD-Serono, Gilead, Lilly, Tyra Biosciences, and Pharmacyclics. He has received honoraria from EMD-Serono, Research to Practice, MJH LifeSciences, Medscape, Uptodate, Clinical Care Options, and OncLive. CR has received research funding (institutional) from Viralytics, Roche, Viralytics/Merck, and Eisai and has participated in a consulting/advisory role with Bristol Myers Squibb. She has received honoraria from Bristol Myers Squibb, Pfizer, Novartis, and Eisai and travel, accommodations, and expenses from Astellas Pharma, Roche, Janssen, GlaxoSmithKline, Bristol Myers Squibb, and Ipsen. DCC has nothing to disclose. BDC has received research funding from Viralytics, Galectin Therapeutics, Clinigen, AstraZeneca (research institution), and Bristol Myers Squibb (research institution). He has participated on the scientific advisory boards of Clinigen, Cullinan Oncology, and Nektar. He is a data safety monitoring board member for Merck USA. JRM has received research funding (institutional) from Sillagen, Vyriad, Replimune, Corvus Pharmaceuticals, Tizona, Trishula Therapeutics, Merck, Eisai, Genentech, Peloton Therapeutics, Seagen, Rubius Therapeutics, and BioNtech. He has participated on the scientific advisory board of Merck. YR is an employee of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, New Jersey, USA, and stockholder in Merck & Co., Inc., Rahway, New Jersey, USA. EVS is an employee of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, New Jersey, USA, and stockholder in Merck & Co. Inc., Rahway, New Jersey, USA. LG is a former contractor to Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, New Jersey, USA, and stockholder in Merck & Co., Inc., Rahway, New Jersey, USA. SG has received honoraria from SITC advances in Cancer Immunotherapy as the Salt Lake City Program Organizer and presenter, travel support from QED Biopharmaceutical, as well as funding for other clinical trials from Bristol Myers Squibb, Rexahn, Incyte, Novartis, LSK, Five Prime, Mirati, QED, Debiopharm, Merck, Pfizer, AstraZeneca, MedImmune, Clovis, Immunocore, Elevar Therapeutics, and Seattle Genetics. |
| References: | J Clin Oncol. 2015 Sep 1;33(25):2780-8. (PMID: 26014293) Lancet. 2016 Apr 9;387(10027):1540-1550. (PMID: 26712084) Ann Surg Oncol. 2010 Mar;17(3):718-30. (PMID: 19915919) Clin Cancer Res. 2019 Oct 1;25(19):5818-5831. (PMID: 31273010) N Engl J Med. 2015 May 21;372(21):2018-28. (PMID: 25891174) Lancet Oncol. 2017 Feb;18(2):212-220. (PMID: 28081914) Clin Cancer Res. 2009 Dec 1;15(23):7412-20. (PMID: 19934295) N Engl J Med. 2017 Mar 16;376(11):1015-1026. (PMID: 28212060) J Virol. 1997 Jun;71(6):4736-43. (PMID: 9151867) N Engl J Med. 2015 Jun 25;372(26):2521-32. (PMID: 25891173) J Clin Oncol. 2021 Dec 1;39(34):3829-3838. (PMID: 34464163) Eur J Cancer. 2009 Jan;45(2):228-47. (PMID: 19097774) N Engl J Med. 2015 Jul 2;373(1):23-34. (PMID: 26027431) J Immunother Cancer. 2020 Oct;8(2):. (PMID: 33046622) Cell. 2017 Sep 7;170(6):1109-1119.e10. (PMID: 28886381) J Hyg (Lond). 1965 Sep;63(3):327-43. (PMID: 5318065) Oncolytic Virother. 2014 Apr 10;3:47-55. (PMID: 27512662) J Clin Oncol. 2019 Oct 1;37(28):2518-2527. (PMID: 31154919) Front Oncol. 2021 Feb 19;10:561372. (PMID: 33680911) Lancet. 2019 May 4;393(10183):1819-1830. (PMID: 30955977) |
| Grant Information: | P30 CA008748 United States CA NCI NIH HHS |
| Contributed Indexing: | Keywords: Immunotherapy; Lung Neoplasms; Oncolytic Virotherapy; Oncolytic Viruses; Urinary Bladder Neoplasms |
| Molecular Sequence: | ClinicalTrials.gov NCT02043665 |
| Substance Nomenclature: | DPT0O3T46P (pembrolizumab) 0 (Antibodies, Monoclonal, Humanized) |
| Entry Date(s): | Date Created: 20230120 Date Completed: 20230124 Latest Revision: 20240105 |
| Update Code: | 20260130 |
| PubMed Central ID: | PMC9872507 |
| DOI: | 10.1136/jitc-2022-005007 |
| PMID: | 36669791 |
| Βάση Δεδομένων: | MEDLINE |
| ISSN: | 2051-1426 |
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| DOI: | 10.1136/jitc-2022-005007 |