TY - JOUR
T1 - Clinical Responses of Oncolytic Coxsackievirus A21 (V937) in Patients with Unresectable Melanoma
AU - Andtbacka, Robert H.I.
AU - Curti, Brendan
AU - Daniels, Gregory A.
AU - Hallmeyer, Sigrun
AU - Whitman, Eric D.
AU - Lutzky, Jose
AU - Spitler, Lynn E.
AU - Zhou, Karl
AU - Bommareddy, Praveen K.
AU - Grose, Mark
AU - Wang, Meihua
AU - Wu, Cai
AU - Kaufman, Howard L.
N1 - Funding Information:
Supported by Viralytics Limited, a wholly owned subsidiary of Merck & Co, Inc, Kenilworth, NJ. The authors thank Darren Shafren, formerly of Viralytics Limited, a wholly owned subsidiary of Merck & Co, Inc, Kenilworth, NJ, for his contributions to the study. The authors also thank Emilee Connors, an employee of Merck Sharp & Dohme Corp, a subsidiary of Merck & Co, Inc, Kenilworth, NJ, for her helpful input during development of the manuscript. Medical writing assistance was provided by Michael S. McNamara, MS, of ICON plc (North Wales, PA). This assistance was funded by Merck Sharp & Dohme Corp, a subsidiary of Merck & Co, Inc, Kenilworth, NJ.
Funding Information:
The authors thank Darren Shafren, formerly of Viralytics Limited, a wholly owned subsidiary of Merck & Co, Inc, Kenilworth, NJ, for his contributions to the study. The authors also thank Emilee Connors, an employee of Merck Sharp & Dohme Corp, a subsidiary of Merck & Co, Inc, Kenilworth, NJ, for her helpful input during development of the manuscript. Medical writing assistance was provided by Michael S. McNamara, MS, of ICON plc (North Wales, PA). This assistance was funded by Merck Sharp & Dohme Corp, a subsidiary of Merck & Co, Inc, Kenilworth, NJ.
Publisher Copyright:
Copyright © 2022 American Society of Clinical Oncology. All rights reserved.
PY - 2021/12/1
Y1 - 2021/12/1
N2 - PURPOSE We evaluated the activity of intratumoral Coxsackievirus A21 (V937) in 57 patients with unresectable stage IIIC or IV melanoma. PATIENTS AND METHODS In this multicenter, open-label, phase II study, patients received up to a total V937 dose of 3 3 108 TCID50 (50% tissue culture infectious dose) in a maximum 4.0-mL volume by intratumoral injection. Ten sets of V937 injections were administered between days 1 and 127 (NCT01227551). Patients who had stable disease or were responding could continue treatment in an extension study (NCT01636882). Response and progression status were based on contrast-enhanced computed tomography, magnetic resonance imaging, or caliper measurement and were categorized using immune-related Response Evaluation Criteria in Solid Tumors (irRECIST). Other evaluations included monitoring of adverse events and serum levels of V937 and anti-V937 antibody titers. The primary efficacy end point was 6-month progression-free survival (PFS) rate per irRECIST. RESULTS The primary efficacy end point, 6-month PFS rate per irRECIST, was 38.6% (95% CI, 26.0 to 52.4). Durable response rate (partial or complete response for $ 6 months) was 21.1% per irRECIST. Best overall response rate (complete plus partial response) was 38.6% (unconfirmed) and 28.1% (confirmed) per irRECIST. Regression of melanoma was observed in noninjected lesions. Based on Kaplan-Meier estimation, 12-month PFS was 32.9% (95% CI, 19.5 to 46.9) per irRECIST and 12-month overall survival was 75.4% (95% CI, 62.1 to 84.7). No treatment-related grade $ 3 adverse events occurred. Viral RNA was detected in serum within 30 minutes of administration. Neutralizing antibody titers increased to . 1:16 in all patients after day 22, without effect on clinical or immunologic response. CONCLUSION V937 was well tolerated and warrants further investigation for treatment of patients with unresectable melanoma. Studies of combination approaches with V937 and immune checkpoint inhibitors are ongoing.
AB - PURPOSE We evaluated the activity of intratumoral Coxsackievirus A21 (V937) in 57 patients with unresectable stage IIIC or IV melanoma. PATIENTS AND METHODS In this multicenter, open-label, phase II study, patients received up to a total V937 dose of 3 3 108 TCID50 (50% tissue culture infectious dose) in a maximum 4.0-mL volume by intratumoral injection. Ten sets of V937 injections were administered between days 1 and 127 (NCT01227551). Patients who had stable disease or were responding could continue treatment in an extension study (NCT01636882). Response and progression status were based on contrast-enhanced computed tomography, magnetic resonance imaging, or caliper measurement and were categorized using immune-related Response Evaluation Criteria in Solid Tumors (irRECIST). Other evaluations included monitoring of adverse events and serum levels of V937 and anti-V937 antibody titers. The primary efficacy end point was 6-month progression-free survival (PFS) rate per irRECIST. RESULTS The primary efficacy end point, 6-month PFS rate per irRECIST, was 38.6% (95% CI, 26.0 to 52.4). Durable response rate (partial or complete response for $ 6 months) was 21.1% per irRECIST. Best overall response rate (complete plus partial response) was 38.6% (unconfirmed) and 28.1% (confirmed) per irRECIST. Regression of melanoma was observed in noninjected lesions. Based on Kaplan-Meier estimation, 12-month PFS was 32.9% (95% CI, 19.5 to 46.9) per irRECIST and 12-month overall survival was 75.4% (95% CI, 62.1 to 84.7). No treatment-related grade $ 3 adverse events occurred. Viral RNA was detected in serum within 30 minutes of administration. Neutralizing antibody titers increased to . 1:16 in all patients after day 22, without effect on clinical or immunologic response. CONCLUSION V937 was well tolerated and warrants further investigation for treatment of patients with unresectable melanoma. Studies of combination approaches with V937 and immune checkpoint inhibitors are ongoing.
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U2 - 10.1200/JCO.20.03246
DO - 10.1200/JCO.20.03246
M3 - Article
C2 - 34464163
AN - SCOPUS:85120808603
VL - 39
SP - 3829
EP - 3838
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
SN - 0732-183X
IS - 34
ER -