@article {Rudine005007, author = {Charles M Rudin and Hardev S Pandha and Matthew Zibelman and Wallace L Akerley and Kevin J Harrington and Daphne Day and Andrew G Hill and Steven J O{\textquoteright}Day and Timothy D Clay and Gavin M Wright and Ross R Jennens and David E Gerber and Jonathan E Rosenberg and Christy Ralph and David C Campbell and Brendan D Curti and Jaime R Merchan and Yixin Ren and Emmett V Schmidt and Lisa Guttman and Sumati Gupta}, title = {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}, volume = {11}, number = {1}, elocation-id = {e005007}, year = {2023}, doi = {10.1136/jitc-2022-005007}, publisher = {BMJ Specialist Journals}, abstract = {Background Oncolytic virus V937 showed activity and safety with intratumoral administration. This phase 1 study evaluated intravenous V937{\textpm}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{\textendash}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.Data are available upon reasonable request. Merck Sharp \& Dohme LLC, a subsidiary of Merck \& Co., Inc., Rahway, New Jersey, USA (MSD), is committed to providing qualified scientific researchers access to anonymized data and clinical study reports from the company{\textquoteright}s clinical trials for the purpose of conducting legitimate scientific research. MSD is also obligated to protect the rights and privacy of trial participants and, as such, has a procedure in place for evaluating and fulfilling requests for sharing company clinical trial data with qualified external scientific researchers. The MSD data sharing website (available at: http://engagezone.msd.com/ds_documentation.php) outlines the process and requirements for submitting a data request. Applications will be promptly assessed for completeness and policy compliance. Feasible requests will be reviewed by a committee of MSD subject matter experts to assess the scientific validity of the request and the qualifications of the requestors. In line with data privacy legislation, submitters of approved requests must enter into a standard data-sharing agreement with MSD before data access is granted. Data will be made available for request after product approval in the USA and European Union or after product development is discontinued. There are circumstances that may prevent MSD from sharing requested data, including country-specific or region-specific regulations. If the request is declined, it will be communicated to the investigator. Access to genetic or exploratory biomarker data requires a detailed, hypothesis-driven statistical analysis plan that is collaboratively developed by the requestor and MSD subject matter experts; after approval of the statistical analysis plan and execution of a data-sharing agreement, MSD will either perform the proposed analyses and share the results with the requestor or will construct biomarker covariates and add them to a file with clinical data that is uploaded to an analysis portal so that the requestor can perform the proposed analyses.}, URL = {https://jitc.bmj.com/content/11/1/e005007}, eprint = {https://jitc.bmj.com/content/11/1/e005007.full.pdf}, journal = {Journal for ImmunoTherapy of Cancer} }