Clinical Responses of Oncolytic Coxsackievirus A21 (V937) in Patients With Unresectable Melanoma

• DOI: 10.1200/jco.20.03246
• Publication Date: 2021-08-31T19:59:25Z
• Authors: Robert H. I. Andt...; Brendan Curti; Gregory A. Daniels; Sigrun Hallmeyer; Eric D. Whitman; Jose Lutzky; Lynn E. Spitler; Karl Zhou; Praveen K. Bommar...; Mark Grose; Meihua Wang; Cai Wu; Howard L. Kaufman
• Keywords: Clinical endpoint

We evaluated the activity of intratumoral Coxsackievirus A21 (V937) in 57 patients with unresectable stage IIIC or IV melanoma.In this multicenter, open-label, phase II study, received up to a total V937 dose 3 × 108 TCID50 (50% tissue culture infectious dose) maximum 4.0-mL volume by injection. Ten sets injections were administered between days 1 and 127 (NCT01227551). Patients who had stable disease responding could continue treatment an extension study (NCT01636882). Response progression status based on contrast-enhanced computed tomography, magnetic resonance imaging, caliper measurement categorized using immune-related Evaluation Criteria Solid Tumors (irRECIST). Other evaluations included monitoring adverse events serum levels anti-V937 antibody titers. The primary efficacy end point was 6-month progression-free survival (PFS) rate per irRECIST.The point, PFS irRECIST, 38.6% (95% CI, 26.0 52.4). Durable response (partial complete for ≥ 6 months) 21.1% irRECIST. Best overall (complete plus partial response) (unconfirmed) 28.1% (confirmed) Regression melanoma observed noninjected lesions. Based Kaplan-Meier estimation, 12-month 32.9% 19.5 46.9) irRECIST 75.4% 62.1 84.7). No treatment-related grade occurred. Viral RNA detected within 30 minutes administration. Neutralizing titers increased > 1:16 all after day 22, without effect clinical immunologic response.V937 well tolerated warrants further investigation melanoma. Studies combination approaches immune checkpoint inhibitors are ongoing.