Peregrine Pharmaceuticals, Inc., a clinical-stage biopharmaceutical company developing first-in-class monoclonal antibodies for the diagnosis and treatment of cancer and viral infections, has initiated an investigator-sponsored trial (IST)  for patients with stage II or stage III rectal adenocarcinoma.

This open-label phase I trial will treat up to 18 patients with Peregrine's investigational monoclonal antibody bavituximab in combination with the chemotherapeutic agent capecitabine and radiation therapy. Peregrine's lead clinical candidate, bavituximab, is a phosphatidylserine (PS)-targeting antibody that has demonstrated promising tumor response and survival trends in randomized phase II trials in non-small cell lung cancer (NSCLC).

“Preclinical studies have repeatedly shown that radiation increases the exposure of bavituximab's target molecule, PS, on the surface of tumor blood vessel cells. Additionally, bavituximab in combination with radiation therapy has demonstrated potent anti-tumor effects in models of lung and brain cancer, with evidence of enhanced immunity," said Jeffrey Meyer, MD, principal investigator of the study and assistant professor of radiation oncology at the University of Texas Southwestern Medical Centre. “We look forward to evaluating this promising treatment combination in patients with advanced rectal cancer.”

Bavituximab is also being evaluated in randomized phase II trials in NSCLC, and pancreatic cancer, as well as multiple ISTs in additional oncology indications.

“Building on consistently promising data in multiple preclinical tumor models, this trial represents our first clinical study of bavituximab combined with radiation,” said Joseph Shan, vice president of clinical and regulatory affairs of Peregrine. “We intend for this trial to be the first step in assessing bavituximab's potential benefit in several additional oncology indications commonly treated with radiation therapy.”

This phase I single-arm, open-label, dose-escalation trial will enroll up to 18 patients with stage II or III rectal adenocarcinoma, with Eastern Cooperative Oncology Group (ECOG) performance status of 0-1. Patients will receive weekly bavituximab for a total of 8 weeks with administration of capecitabine (825 mg/m2) on each of the 28 days of radiation therapy (1.8 Gy/fraction) over 6 weeks, followed by two weeks of bavituximab administration by itself. Surgery will follow the last bavituximab administration by four to eight weeks (i.e., six-10 weeks following completion of radiation therapy). The primary endpoint is to determine the safety, feasibility and tolerability of combining bavituximab with a standard platform of capecitabine and radiation therapy. Secondary endpoints include the assessment of any anti-tumor activity by objective response as determined by MR imaging and histopathological response in patients.

This trial is being conducted by the  University of Texas-Southwestern Medical Centre.

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 tumor blood vessels, creating a specific target for anti-cancer treatments. PS-targeting antibodies target and bind to PS and block this immunosuppressive signal, thereby enabling the immune system to recognize and fight the tumour.

Peregrine's IST programme offers oncologists the opportunity to conduct clinical trials with bavituximab.

According to the National Cancer Institute (NCI), approximately 50,000 new cases of rectal adenocarcinoma will be diagnosed in 2012. The five-year survival rate for Stage IV rectal cancer is estimated to be six per cent