Final data from CALM: A phase II study of Coxsackievirus A21 (CVA21) oncolytic virus immunotherapy in patients with advanced melanoma.

9030 Background: CVA21 (CAVATAK) is a novel bio-selected oncolytic and immunotherapeutic strain of Coxsackievirus A21. Intratumoral (i.t) CVA21 injection initiates preferential tumor cell infection, cell lysis and enhancement of a systemic anti-tumor immune response. Presented are the final data of the open-label, multicenter Phase II CALM (CAVATAK in Late stage Melanoma) study. Methods: The CALM study investigated the efficacy and safety of i.t CVA21 in 57 patients with treated or untreated unresectable Stage IIIC-IVM1c melanoma. Pts received up to 3 x 108 TCID50CVA21 i.t on study days 1,3,5, 8 and 22, and then every three weeks for a further 6 injections. Pts displaying immune-related progression-free survival (irPFS) or better at 6 mos were eligible for 9 additional injections. Key eligibility criteria were ≥ 18 yrs old, ECOG PS 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 pts with irPFS at 6 mos. Secondary endpoints included irRECIST overall response rate, durable response rate (continuous response ≥ 6mos), median time to response and 1-year survival. Results: The primary endpoint of the study was achieved with 21 of 57 (38.6%) evaluable pts displaying irPFS at 6 mos with a median irPFS of 4.2 mos. The overall response rate (irRECIST) was 28.1% (16 of 57 evaluable pts) with a ≥ 6 mos durable response rate of 19.3 % (11 of 57 pts). The median time to response was 2.8 mos, and the 1-year survival rate 75.4% (43 of 57 pts). After a median follow-up of ~16.5 mos, median duration of response in responders and median OS for all pts was not reached. The most common AE’s were Grade 1 fatigue, chills, local injection site reactions and fever. No Grade 3 or 4 product-related AE’s were observed. Conclusions: Intralesional CVA21 is a promising novel oncolytic immunotherapeutic agent for the treatment of unresectable Stage IIIC-IVM1c melanoma and the CALM study met its primary endpoint of irPFS at 6 mos. CVA21 was well tolerated and exhibited both local and distant durable tumor responses. Further clinical studies using CVA21 in combination with other immunotherapies are underway. Clinical trial information: NCT01227551.