1103P - CALM study: Secondary endpoints of a Phase II study of a novel oncolytic immunotherapeutic agent, coxsackievirus A21, delivered intratumorally in p...

Date 28 September 2014
Event ESMO 2014
Session Poster Display session
Topics Immunotherapy
Skin Cancers
Presenter Robert Andtbacka
Citation Annals of Oncology (2014) 25 (suppl_4): iv374-iv393. 10.1093/annonc/mdu344
Authors R.H. Andtbacka1, B. Curti2, H. Kaufman3, G.A. Daniels4, J.J. Nemunaitis5, L.E. Spitler6, S. Hallmeyer7, J. Lutzky8, S. Schultz9, E.D. Whitman10, K. Zhou11, J.I. Weisberg12, D. Shafren12
  • 1Surgical Oncology, Huntsman Cancer Institute, 84112 - Salt Lake City/US
  • 2Medical Oncology, Providence Cancer Center, Portland/US
  • 3Surgical Oncology, Rush University Medical Center, Chicago/US
  • 4Medical Oncology, UCSD Moores Cancer Center, San Diego/US
  • 5Medical Oncology, Mary Crowley Cancer Research Center, Dallas/US
  • 6Medical Oncology, Northern California Melanoma Center, San Francisco/US
  • 7Medical Oncology, Oncology Specialists SC, Park Ridge/US
  • 8Medical Oncology, Mount Sinai Comprehensive Cancer Center, Miami Beach/US
  • 9Medical Oncology, Investigative Clinical Research, Indianapolis/US
  • 10Surgical Oncology, Atlantic Melanoma Center,, Morristown/US
  • 11Oncology, Pharmanet/i3, Princeton/US
  • 12Oncology, Viralytics,, Sydney/AU



CAVATAK, an oncolytic immunotherapy, is a bio-selected oncolytic strain of Coxsackievirus A21. Following intratumoral injection, CAVATAK preferentially infects ICAM-1 expressing tumor cells, resulting in cell lysis and a systemic anti-tumor immune response. We here report on the key secondary endpoints in the Phase II CALM study.


The CALM study investigated the efficacy and safety of intratumoral CAVATAK in 57 patients with treated or untreated unresectable Stage IIIC-IVM1c melanoma. Patients received up to 3 x 108 TCID50 CAVATAK intratumorally 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 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. Secondary endpoints included median irPFS, 1-year survival, median time to response, irRECIST 1.1 best overall response (BORR) and safety.


The primary endpoint of the study was achieved with 19 of 51 (37.3%) evaluable patients displaying irPFS at 6 months. Preliminary analysis of secondary endpoints showed: median irPFS of 4.2 months (95% CI 2.8, 8.3), 1-year survival 61.5% (16 of 26 pts), on-going BORR (irRECIST 1.1) 26.3% (15 of 57 pts) with responses seen in both injected and non-injected lesions, median time to response 2.8 months. To date 15 patients have received additional series of CAVATAK injections. The most common patient side effects observed were Grade 1 local injection site reactions, fatigue, chills and fever. There were no Grade 3 or 4 product-related AE's.


Intralesional CAVATAK is a promising novel oncolytic immunotherapeutic agent with limited toxicity and robust responses in both injected and non-injected lesions in patients with advanced melanoma. The effectiveness of CAVATAK warrants additional investigation as monotherapy and in combination with other targeted immunotherapies such as immune checkpoint blockade.


R.H. Andtbacka: Travel honorarium–Viralytics; K. Zhou: Salary - Viralytics J.I. Weisberg: Salary–Viralytics; D. Shafren: Stock, salary–Viralytics. All other authors have declared no conflicts of interest.