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

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 × 10 ⁸ TCID ₅₀ (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.
Competing Interests: Robert H. I. AndtbackaEmployment: Novartis, Merck Sharp & Dohme, Seven and Eight BiopharmaceuticalsStock and Other Ownership Interests: Novartis, Merck Sharp & Dohme Brendan CurtiHonoraria: Clinigen Group, NektarConsulting or Advisory Role: MerckResearch Funding: Bristol Myers Squibb, Galectin Therapeutics, Clinigen GroupPatents, Royalties, Other Intellectual Property: Biomarkers for OX40 responseTravel, Accommodations, Expenses: Agonox Gregory A. DanielsHonoraria: Sanofi/RegeneronConsulting or Advisory Role: Sanofi/RegeneronSpeakers' Bureau: Regeneron, Array BioPharma, Sanofi/RegeneronResearch Funding: Bristol Myers Squibb, Amgen, Viralytics, Nektar, Merck Sigrun HallmeyerLeadership: Association of Community Cancer Centers (ACCC)Honoraria: Cardinal HealthConsulting or Advisory Role: Bristol Myers Squibb, Cardinal Health, Array PharamceuticalSpeakers' Bureau: Bristol Myers SquibbTravel, Accommodations, Expenses: Cardinal Health, Bristol Myers SquibbUncompensated Relationships: Society for Immunotherapy of Cancer Eric D. WhitmanConsulting or Advisory Role: Merck Sharp & Dohme, Bristol Myers Squibb, Castle Biosciences, Novartis, Eisai, PfizerSpeakers' Bureau: Bristol Myers Squibb, Merck Sharp & Dohme, Castle Biosciences, Sanofi/RegeneronResearch Funding: Bristol Myers Squibb, Merck Sharp & Dohme, Castle Biosciences, Genentech/Roche, Amgen, TRACON Pharma, AstraZeneca/MedImmune, Provectus, Oncolys BioPharma, Iovance Biotherapeutics, Dynavax Technologies, OncoSec, Toray Industries, Array BioPharmaPatents, Royalties, Other Intellectual Property: Nerve monitoring dissection device, Lighted Polyhedral surgical retractor Jose LutzkyConsulting or Advisory Role: Castle Biosciences, Iovance Biotherapeutics, Replimune, RegeneronResearch Funding: Bristol Myers Squibb, Novartis, Iovance Biotherapeutics, Immunocore, Regeneron, Replimune, Vyriad Lynn E. SpitlerLeadership: Nuclear RNA Networks IncStock and Other Ownership Interests: Nuclear RNA Networks Inc Praveen K. BommareddyEmployment: ReplimuneStock and Other Ownership Interests: Replimune Mark GroseConsulting or Advisory Role: ImmVirX Meihua WangEmployment: MerckStock and Other Ownership Interests: Merck Cai WuEmployment: Merck (at the time the work was conducted)Stock and Other Ownership Interests: Merck Sharp & Dohme Howard L. KaufmanEmployment: ImmuneeringLeadership: ImmuneeringStock and Other Ownership Interests: ImmuneeringHonoraria: Society for Immunotherapy of CancerNo other potential conflicts of interest were reported.