Vical Demonstrates Safety And Tolerability Of IL-2 DNA Delivery With Electroporation

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Vical Incorporated announced data from an ongoing Phase 1 clinical trial demonstrated that intratumoral delivery of plasmid DNA encoding interleukin-2 into melanoma tumors, followed by electroporation, was administered safely following sedative premedication.

No serious adverse events related to the study drug or to the administration procedure were reported and the treatment was well-tolerated. The majority of related adverse events were localized to the treatment site, with the most frequent being mild injection site pain.

Individual tumor responses were seen in 12 of 39 (31%) evaluated tumors after injection of different escalating doses (0.5 to 5 mg per tumor). Treated tumors (7 of 18, or 38%) showed local responses more frequentlythan did untreated tumors (5 of 21, or 24%). No overall clinical responses by standard RECIST criteria were observed among the 19 subjects evaluated following one or two cycles of treatment. Two subjects (11%) showed activity in distant, untreated tumors, including one subject showing shrinkage and disappearance of lung tumors. The data were presented at the annual meeting of the American Society of Clinical Oncology (Chicago, June 1 - 5) by Jon M. Richards, M.D., Ph.D., Lutheran General Hospital Division of Hematology/Oncology.

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"The primary objective of our ongoing IL-2/electroporation study is to evaluate the safety and tolerability of electroporation," said Ronald B. Moss, M.D., Vical's Vice President of Clinical Research, "and the interim results appear to support its potential value in advanced cancer or other serious diseases. The need for premedication would limit the use of the current electroporation technology in less serious disease applications. We will monitor data from additional subjects, some of whom are already enrolled but have not yet completed therapy, as well as the secondary efficacy endpoints in this study on a longer-term basis, and evaluate whether further development of the IL-2 product is warranted."

A recent publication by Vical researchers (Cancer Therapy, Vol. 5, 125-132, 2007) reported that mice bearing melanoma tumors below the skin and receiving electroporation following intratumoral administration of IL-2 pDNA had significant reductions in tumor growth compared with mice treated by IL-2 pDNA alone. In addition, 60% of the mice receiving IL-2 pDNA with electroporation became tumor-free, compared with 20% of the mice receiving IL-2 pDNA without electroporation. In a separate study reported in the same publication, mice bearing sarcoma tumors in the skin were evaluated for subsequent metastatic tumors in the liver. IL-2 pDNA treatment of the primary tumor with electroporation resulted in a significant reduction in subsequent metastatic tumor growth compared with IL-2 pDNA treatment alone. Among mice whose primary tumor was treated with IL-2 pDNA with electroporation, 65% had two or fewer subsequent metastatic tumors in the liver. Among mice treated with IL-2 pDNA without electroporation, none had two or fewer subsequent liver metastases, and 55% had liver metastases that were too numerous to count.

The Phase 1 study is evaluating an investigational method of delivering IL-2, a potent immune system stimulant, to subjects with recurrent metastatic melanoma. Intravenous delivery of IL-2 protein is approved as a treatment for metastatic melanoma, but frequently causes severe systemic toxicities. The novel treatment approach being studied in this Phase 1 trial involves direct injection into a tumor of pDNA encoding IL-2 followed by electroporation, the local application of electrical pulses designed to enhance the uptake of the pDNA into tumor cells. The pDNA is designed to cause cells within the tumor to produce high levels of IL-2 protein locally and stimulate the immune system to attack the tumor without the associated systemic toxicities.

Treatments in the trial are administered once a week in two four-week cycles, with each cycle followed by an observation period. The initial dose-escalation phase of the trial enrolled three subjects each at doses of 0.5 mg, 1.5 mg and 5 mg delivered to a single tumor per subject, with a final group receiving 5 mg in each of three tumors per subject. Additional subjects are treated at the highest dose of 5 mg per tumor in up to three injectable tumors.

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