Peregrine Pharmaceuticals Announces Investigator-Sponsored Trial Combining Immunotherapy Bavituximab, Ipilimumab

Peregrine Pharmaceuticals, Inc.

today announced the opening of an investigator-sponsored trial (IST) of its investigational immunotherapy bavituximab in combination with Bristol-Myers Squibb's ipilimumab (Yervoy®), for the treatment of advanced melanoma. Bavituximab is an upstream immune checkpoint inhibitor that targets phosphatidylserine (PS), a highly immunosuppressive molecule exposed on cells that line tumor blood vessels and tumor cells. Preclinical data in a model of melanoma demonstrate that the combination of a bavituximab equivalent and ipilimumab yield enhanced anti-tumor activity compared to ipilimumab alone. The trial is being conducted at the University of Texas Southwestern Medical Center, Dallas, and led by Arthur E. Frankel, M.D., Associate Professor of Internal Medicine at the Simmons Comprehensive Cancer Center. Bavituximab, Peregrine's lead immuno-oncology candidate, is being evaluated in second-line non-small cell lung cancer (NSCLC), as part of the SUNRISE pivotal Phase III clinical trial. "We are pleased that this leading melanoma specialist is advancing this program into clinical development, recognizing that there are patients who may not respond to the current standard of care and that the combination of ipilimumab and bavituximab could potentially elicit anti-tumor immune responses in a larger proportion of patients," said Joseph Shan, MPH, vice president of clinical and regulatory affairs at Peregrine. "We are particularly excited as this trial is designed to provide proof-of-concept data for this potentially innovative upstream and downstream checkpoint inhibitor combination. In addition, the trial's open-label design allows for the potential for data readouts throughout the course of the trial." This is an open label, two-arm, randomized, single-center Phase Ib trial of bavituximab plus ipilimumab (Yervoy®), in patients with advanced melanoma. Up to 24 patients will be randomized into the following two treatment groups: Group A will enroll up to 16 patients to receive 2 weekly doses of bavituximab (3mg/kg) followed by combination therapy of ipilimumab (up to four cycles at 3mg/kg every 3 weeks) plus bavituximab (3mg/kg weekly for 12 weeks) Group B will enroll up to 8 patients to receive standard ipilimumab alone (up to four cycles at 3mg/kg every 3 weeks) The primary endpoint of the trial will be safety and secondary endpoints will include measurements of disease control rate (DCR) and overall survival (OS). In addition, tumor biopsies will be collected at screening to measure changes in myeloid-derived suppressor cells (MDSC), tumor-associated macrophages (TAM), T-regulatory cells (Treg) and peripheral blood cytokines. For more information on this trial please visit ClinicalTrials.gov using the identifier NCT01984255. Preclinical Combination Data of PS-Targeting Antibody and Anti-CTLA-4 Antibody Preclinical data have shown that phosphatidylserine (PS)-targeting antibodies reactivate tumor immunity at multiple levels and that the combination of a PS-targeting antibody equivalent to bavituximab and an anti-CTLA-4 antibody, an FDA-approved immunotherapy, resulted in superior tumor growth inhibition than with either antibody alone, with no additional toxicity following multiple treatment doses. In addition, histopathological analysis showed the combination produced more inflammatory cell infiltration and tumor destruction than anti-CTLA-4 alone. About Melanoma Melanoma is an aggressive and serious form of skin cancer that while generally considered to be preventable and treatable upon early detection, can be fatal if not diagnosed.(1,2) Advanced melanoma occurs when the cancer cells spread through the lymph nodes to other parts of the body. By 2019, worldwide cases of melanoma are expected to double to more than 227,000 from current levels.(3) According to the National Cancer Institute; in 2013 more than 76,000 new cases of melanoma were diagnosed in the United States.(4) About Bavituximab: A Targeted Immunotherapy 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 tumor. These data, detailing the immune-stimulatory mechanism of action of PS-targeting antibodies, such as the company's lead drug candidate bavituximab, are the subject of a manuscript published in the October 2013 issue of the American Association for Cancer Research (AACR) peer-reviewed journal, Cancer Immunology Research. As part of the SUNRISE trial, bavituximab is being evaluated in a Phase III, global, randomized, double-blind, placebo-controlled clinical trial designed to evaluate the safety, tolerability and efficacy of bavituximab plus docetaxel as second-line treatment in patients with non-small cell lung cancer. Bavituximab is also currently being evaluated in several solid tumor indications, including breast cancer, liver cancer and rectal cancer. For additional information about the SUNRISE trial please visit www.SunriseTrial.com or ClinicalTrials.gov using Identifier NCT01999673. About SUNRISE Trial: SUNRISE is a pivotal Phase III, randomized, placebo-controlled, double-blind, multinational clinical trial evaluating the efficacy and safety of bavituximab (bav i tux' i mab), a novel investigational immunotherapy, plus docetaxel versus placebo plus docetaxel as a second-line treatment for patients with Stage IIIb/IV non-squamous non-small cell lung cancer (NSCLC). For more information about the SUNRISE trial, please visit: www.SunriseTrial.com