Peregrine Pharmaceuticals, Inc. a clinical-stage biopharmaceutical company developing first-in-class monoclonal antibodies for the treatment of cancer and viral infections,  announced that its phosphatidylserine (PS)-targeting antibody significantly enhanced the anti-tumour effects of sorafenib (Nexavar) in models of Hepato-Cellular Carcinoma (HCC), with 69% less tumour growth compared to sorafenib alone.

The study, one of four poster presentations on Peregrine's PS-targeting antibodies at the Annual Meeting of the American Association of Cancer Research (AACR), was the basis for initiating a phase I/II Investigator-Sponsored Trial (IST) evaluating the company's lead antibody bavituximab with sorafenib in patients with advanced HCC. Bavituximab is currently in three randomized phase II clinical trials in lung cancer and pancreatic cancer and several ISTs for additional oncology indications.

“Our studies show that sorafenib more than doubles the amount of the immunosuppressive molecule PS exposed on the blood vessels of HCC tumours,” said Philip E Thorpe, PhD, professor of pharmacology at UT Southwestern Medical Centre, scientific adviser to Peregrine and inventor of the company's PS-targeting antibody technology. “These data suggest that the growth-blocking mechanisms of sorafenib combined with the vascular-targeting and immune-reactivation mechanisms of bavituximab may offer additive anti-tumour effects for patients with HCC.”

As presented at AACR, tumour growth was 69% less for the group receiving Peregrine's antibody in combination with sorafenib than for the group receiving sorafenib alone (mean tumour weight of 127 mg versus 409 mg, n=10, p < 0.01) after 59 days of treatment in an animal model study. Immunofluorescence analysis showed that treatment with Peregrine's antibody in combination with sorafenib decreased tumour blood vessel density from 14.2% to 4.5% (p < 0.01), versus 10.3% (p < 0.05) for Peregrine's antibody or 8.4% (p < 0.01) for sorafenib alone.

In an ongoing open-label phase I/II trial, patients with advanced HCC are receiving bavituximab weekly and sorafenib (400 mg) twice daily, until disease progression or toxicity. phase I of the trial is dose escalation (0.3, 1 or 3 mg/kg) to determine the maximum tolerated dose (MTD) and phase II is expansion of the study at the MTD. Approximately 50 patients are being enrolled in this trial, which is being conducted at UT Southwestern Medical Centre.

Primary objectives are to determine the MTD of bavituximab in patients with advanced HCC treated with sorafenib and the radiographic median time to progression. Secondary objectives include response rate, progression free-survival, overall survival, safety and tolerability.

Peregrine's IST programme offers oncologists the opportunity to conduct clinical trials using bavituximab in solid tumour indications.

Bavituximab is a first-in-class phosphatidylserine (PS)-targeting monoclonal antibody that represents a new approach to treating cancer. PS is a highly immunosuppressive molecule usually located inside the membrane of healthy cells, but "flips" and becomes exposed on the outside of cells that line tumour blood vessels, creating a specific target for anti-cancer treatments.

According to the National Cancer Institute, primary liver and bile duct cancers are the sixth most common cause of cancer death in men, and ninth most common in women. Approximately 24,000 new cases of these two cancers are expected to be diagnosed this year in the United States, with approximately 19,000 deaths attributable to these forms of cancer. The most common risk factor for liver cancer is chronic Hepatitis C Virus (HCV) or Hepatitis B Virus (HBV) infection. Currently approved treatment options for HCC are surgery, radiation, chemotherapy, targeted therapeutics, tumour ablation, and tumour embolization.
Xiaoyun Cheng and Philip E. Thorpe, UT Southwestern Medical Centre, Dallas, TX. Phosphatidylserine-targeting antibody combined with sorafenib has strong anti-tumour activity against human hepatocellular carcinomas in mice. In Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research (AACR); 2011 Apr 2-6; Orlando, Florida.

Peregrine Pharmaceuticals, Inc. is pursuing multiple clinical programs in cancer and HCV infection with its lead product candidate bavituximab and novel brain cancer agent Cotara.