Positive results from Allovectin-7 Phase 3 trial in patients with metastatic melanoma

Vical Incorporated today announced a new publication summarizing results from the company's completed trials of Allovectin-7^® including systemic responses and an excellent safety profile in patients with metastatic melanoma. An article published in the January issue of Immunotherapy noted that the U.S. incidence of melanoma is increasing rapidly, that current therapies are inadequate and toxic, and that melanoma is responsive to immune-stimulating drugs like Allovectin-7^®. A Phase 3 trial evaluating the safety and efficacy of Allovectin-7^® compared with standard chemotherapy is expected to complete final follow-ups later this year.

The most recently completed Phase 2 trial was a single-arm, open-label study in which 127 chemo-refractory or chemo-intolerant subjects were treated with high-dose Allovectin-7^®. There were no treatment-related Grade 3 or Grade 4 adverse events, and no withdrawals from the trial for tolerability. The overall response rate for the 127 patients receiving the high-dose treatment was 11.8%, with 4 complete responders and 11 partial responders. The median duration of response was 13.8 months and median survival was 18.8 months. These data compare favorably against historical controls from other studies in metastatic melanoma.

Findings from the Phase 2 trial were incorporated into the design of a Phase 3 pivotal trial through a Special Protocol Assessment agreement with the U.S. Food and Drug Administration (FDA):

• The Phase 3 trial sought patients likely to have functional immune systems.

• Vical's Phase 3 trial was among the first for metastatic melanoma to exclude patients with elevated levels of lactate dehydrogenase (LDH), a key biomarker predictive of prognosis.
• The trial excluded patients previously treated with chemotherapy.

• The Phase 3 trial sought patients healthy enough to remain on study for at least two 8-week treatment cycles, the median time to response in the Phase 2 study.

• The trial excluded patients with metastases to the brain or liver.
• Response Evaluation Criteria In Solid Tumors (RECIST) standards were modified for the Phase 3 protocol to allow treatment continuation through two cycles at the physician's discretion, even if patients develop new melanoma lesions within defined limits.

• Vical's Phase 3 trial was designed to capture the long-term benefits of immunotherapy compared with chemotherapy, as all responses in the Phase 2 trial were durable (≥ 6 months).

• The primary endpoint compares overall response rates at 24 weeks or more after randomization.
• The study will also evaluate survival as well as safety and tolerability.

The Phase 3 trial, initiated in January 2007, is evaluating Allovectin-7^® as first-line therapy in patients with Stage III or IV recurrent metastatic melanoma. Vical completed enrollment in February 2010 of approximately 390 chemo-naive patients randomized on a 2:1 basis: approximately 260 for treatment with Allovectin-7^® and approximately 130 for treatment with either dacarbazine or temozolomide. The company expects to complete patient follow-up and lock the Phase 3 clinical trial database in the second half of 2011.