CALM study: A phase II study of an intratumorally delivered oncolytic immunotherapeutic agent, coxsackievirus A21, in patients with stage IIIc and stage IV malignant melanoma.

Developmental Therapeutics - Immunotherapy
Session Type and Session Title: 
Poster Highlights Session, Developmental Therapeutics - Immunotherapy
Abstract Number: 
J Clin Oncol 32:5s, 2014 (suppl; abstr 3031)
Robert Hans Ingemar Andtbacka, Brendan D. Curti, Howard Kaufman, Gregory A. Daniels, John J. Nemunaitis, Lynn E. Spitler, Sigrun Hallmeyer, Jose Lutzky, Stephen Schultz, Eric D. Whitman, Karl Zhou, Jeffrey Ira Weisberg, Darren Shafren; Huntsman Cancer Institute, University of Utah, Salt Lake City, UT; Earle A. Chiles Research Institute, Portland, OR; Rush University Medical Center, Chicago, IL; UC San Diego Moores Cancer Center, La Jolla, CA; Mary Crowley Cancer Research Centers, Dallas, TX; Northern California Melanoma Center, San Francisco, CA; Oncology Specialists, SC, Niles, IL; Mount Sinai Comprehensive Cancer Center, Miami Beach, FL; Investigative Research Center, Indianapolis, IN; Atlantic Melanoma Center, Morristown, NJ; I3 Research, Princeton, NJ; Viralytics, Ltd., Sydney, Australia

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Abstract Disclosures


Background: Coxsackievirus A21 is an oncolytic immunotherapy consisting of a bio-selected oncolytic strain of Coxsackievirus A21. Following intratumoral injection, preferential tumor infection causes cell lysis and enhancement of a systemic anti-tumor immune response. We present interim findings of the open-labeled, multicenter Phase II Coxsackievirus A21 in Late stage Melanoma (CALM) study. Methods: The CALM study investigated the efficacy and safety of intratumoral Coxsackievirus A21 in 57 patients with treated or untreated unresectable Stage IIIC-IVM1c melanoma. Patients received up to 3 x 108 TCID50Coxsackievirus A21intratumorally on study days 1,3,5 and 8 and then every three weeks for a further 6 injections. Patients displaying immune-related progression-free survival (irPFS) or better at 6 months were eligible for 9 additional injections. Key eligibility criteria were ≥ 18 yrs old, ECOG 0-1, and at least 1 injectable cutaneous, subcutaneous, or nodal melanoma metastasis >1.0 cm. The primary endpoint was to achieve >9 of 54 evaluable patients with irPFS at 6 months. The irPFS was calculated as the proportion of patients demonstrating a Complete Response, Partial Response or Stable Disease by immune-related RECIST 1.1 (irRECIST 1.1) criteria 6 months after the initiation of treatment. Secondary endpoints included 1-year survival, irRECIST1.1 best overall response and safety. Results: The primary endpoint of the study was achieved with 14 of 40 (35%) evaluable patients displaying irPFS at 6 months. The number of patients surviving 1-year from the initial treatment is 13 of 21 (62%). Best overall response rate (irRECIST 1.1) is 24% (9 of 38 evaluable patients). Patients received on average 8.3 series of injections, with the most common side effects being Grade 1 fatigue, chills, local injection site reactions and fever. There were no Grade 3 or 4 product-related AE’s. Conclusions: Intralesional Coxsackievirus A21 is a promising novel oncolytic immunotherapeutic agent in the treatment of unresectable Stage IIIC-IV M1c melanoma based on good patient tolerability, with both local and distant tumor responses. A randomized phase 2 clinical trial is planned. Clinical trial information: NCT01227551.