Vical Incorporated announced encouraging animal data demonstrating a synergistic (more than additive) improvement in efficacy using a combination of the company's Allovectin immunotherapy with an anti-CTLA-4 antibody.

Treatment with Allovectin plus anti-CTLA-4 antibody provided a synergistic reduction of tumour growth compared with either treatment alone (both p<0.001).

Synergy became evident about 12 days after treatment initiation, suggesting a likely two-step process in which Allovectin first directs T cells to target the melanoma tumour and anti-CTLA-4 antibody then maximally activates these T cells.

Treatment with Allovectin plus anti-CTLA-4 antibody provided a positive trend in survival compared with either treatment alone.

Allovectin alone significantly reduced tumour growth and significantly increased survival time compared with anti-CTLA-4 antibody treatment alone and compared with no treatment (all p<0.001).

"We expected a synergistic effect with this co-treatment, and were pleased that this study confirmed it," said Alain P. Rolland, Pharm.D., Ph.D., Vical's executive vice president of product development. "Allovectin directs a potent and multifaceted systemic immune response against the target cancer cells, and anti-CTLA-4 antibodies drive the activation of additional T cells. Together, these complementary therapies can provide a powerful one-two punch."

The study was conducted in a well-accepted melanoma mouse model using a standard mouse equivalent of human anti-CTLA-4 antibodies such as ipilimumab. Cohorts included untreated mice, mice treated with Allovectin alone, mice treated with anti-CTLA-4 antibody alone, and mice treated with Allovectin plus anti-CTLA-4 antibody. Dosing for Allovectin was a single cycle of once per day for the first four days. Dosing for the anti-CTLA-4 antibody was once every three days for the duration of the study. The study tracked growth of implanted melanoma tumours and survival. Results were encouraging and support further evaluation of such combination treatment in human clinical trials.

John Doukas, Ph.D., Vical's senior director of pre-clinical safety and efficacy, presented the results, "Synergistic Anti-Tumour Efficacy Using Allovectin and Anti-CTLA-4 Combination Immunotherapy in a Murine Melanoma Model," at the National Cancer Institute Conference on Cancer Immunology and Immunotherapy: Building on Success (Bethesda, MD – September 22-23).

Allovectin is a systemic immunotherapeutic with a unique mechanism of action that may be complementary to currently approved treatments. It is delivered into a single tumour lesion, but elicits an immune response directed against lesions throughout the body. Among patients with more than one lesion at baseline in a completed high-dose phase 2 study, 57% of clinical responders and 17% of clinical nonresponders had tumour responses in noninjected lesions. Vical's ongoing Phase 3 trial is evaluating Allovectin compared with standard chemotherapy as a first-line therapy in patients with Stage III or IV recurrent metastatic melanoma. The primary endpoint is objective response rate at 24 weeks or more after randomization, and overall survival is a secondary endpoint. Vical completed enrollment in February 2010 of 390 chemo-naive patients randomized on a 2:1 basis for treatment with Allovectin or chemotherapy (physician's choice of either dacarbazine or temozolomide). The company expects to complete treatment and follow-up for the primary endpoint in the Phase 3 trial by February 2012, with continued monitoring for the secondary endpoint up to the release of top-line data for both endpoints in the second quarter of 2012.

Allovectin has demonstrated an excellent safety profile in multiple clinical trials. In the high-dose Phase 2 trial, there were no grade 3 or grade 4 drug-related adverse events. Safety has been a hallmark of Allovectin treatment, and side effects typically have been local and not significant.

Vical researches and develops biopharmaceutical products based on its patented DNA delivery technologies for the prevention and treatment of serious or life-threatening diseases.