TUSTIN, Calif.—Peregrine Pharmaceuticals Inc., a biopharmaceutical company focused on developing therapeutics to stimulate the body's immune system to fight cancer, has provided a clinical development update for bavituximab, the company’s investigational phosphatidylserine (PS)-targeting immunotherapy. In the first quarter of 2016, Peregrine plans to initiate two new Phase 2 clinical trials in breast and lung cancer in combination with current standard of care treatments including both chemotherapy and immuno-oncology agents. In addition, the company has entered into a collaboration with the National Comprehensive Cancer Network (NCCN) to evaluate bavituximab in other tumor types and combinations. Also, the company is nearing completion of enrollment of an ongoing Phase 3 trial in non-small cell lung cancer (NSCLC) named SUNRISE.
The planned trials include a Phase 2 NSCLC trial in combination with AstraZeneca’s investigational anti-PD-L1 immune checkpoint inhibitor, durvalumab (MEDI4736), and a Phase 2 trial in early stage triple negative breast cancer (TNBC). These are in addition to the recently initiated Phase 2/3 study in combination with chemotherapy in human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (MBC). The company expects that initial data from these trials may be available in late 2016 or early 2017. Additionally, the company looks forward to the initiation of additional trials of bavituximab combinations through its ongoing collaborations with AstraZeneca and NCCN.
“As we wrap up enrollment in the SUNRISE trial, we recognize that we are at an ideal juncture to continue expanding the potential of bavituximab with standard of care and immunotherapy combinations in multiple solid tumor types. Combined with the SUNRISE trial, the new studies we have planned can help solidify the potential of bavituximab in NSCLC while significantly expanding the market opportunity in breast cancer,” said Steven W. King, president and CEO of Peregrine. “Driving our strategy is the goal of further demonstrating that bavituximab can provide therapeutic benefit to available cancer treatments, regardless of whether those are traditional therapies such as chemotherapy and radiation, or the emerging novel class of immuno-oncology agents. In today’s update, it is evident that we are moving aggressively to compile a significant body of clinical evidence to support bavituximab’s utility in multiple cancers and across a range of treatment regimens. By doing so, we hope to optimally position bavituximab for success.”
Bavituximab is an investigational immunotherapy designed to assist the body's immune system by targeting and modulating the activity of phosphatidylserine (PS), a highly immune-suppressive signaling molecule expressed broadly on the surface of cells in the tumor microenvironment. Peregrine’s PS targeted inhibitor, bavituximab, is thought to reverse the immunosuppressive environment that many tumors establish in order to proliferate and spread, while also fighting cancer by activating immune cells that target and fight cancer.
Updated details on Peregrine’s expanded bavituximab clinical development program include:
Peregrine’s Phase 3 SUNRISE (Stimulating ImmUne RespoNse thRough BavItuximab in a PhaSE III Lung Cancer Study) trial is evaluating the use of bavituximab and docetaxel in patients with previously treated locally advanced or metastatic non-squamous NSCLC. Peregrine expects that the first interim analysis (33 percent of targeted number of deaths) will be conducted in early 2016 and the second interim analysis (50 percent of targeted number of deaths) in mid-2016. The final analysis, which will trigger the unblinding of the study data, is currently projected to occur at the end of 2016.
Peregrine expects to initiate a global Phase 2 study of bavituximab in combination with AstraZeneca’s durvalumab, an anti-PD-L1 immune checkpoint inhibitor, in patients with previously treated squamous or non-squamous NSCLC during the first quarter of 2016. The goal of this trial is to generate data on the combination of bavituximab and durvalumab to inform the potential advancement of this treatment regimen into later stage clinical trial. The study’s primary endpoints are overall response rate (ORR) and safety. The trial is also designed to retrospectively evaluate patients for the correlation between their PD-L1 levels and clinical outcomes, providing further critical data to guide future development.
The randomized, open-label trial will evaluate approximately 200 patients at sites in the U.S. and Europe. The company has filed a study protocol to its existing investigational new drug (IND) application for bavituximab in the U.S. and is currently working to open clinical trial sites.
In December 2015, Peregrine initiated an open-label, randomized Phase 2/3 study comparing the efficacy and safety outcomes for taxane monotherapy (paclitaxel or docetaxel at investigator discretion) versus taxane therapy in combination with bavituximab in HER2-negative MBC patients. The goal of the Phase 2 portion of this study is to generate mature data on the combination of bavituximab and chemotherapy in MBC to guide the design and execution of the trial’s Phase 3 component. The primary efficacy endpoint of the Phase 2 study is ORR, with secondary endpoints including progression free survival (PFS), overall survival (OS), duration of response and safety. The Phase 2 portion of the study will enroll approximately 150 patients at sites in the U.S. and Europe.
Peregrine is also planning to initiate a Phase 2 trial of bavituximab in combination with neoadjuvant chemotherapy in early stage TNBC. The primary endpoint of this study is to determine the pathologic complete response rate (pCR), an accepted surrogate endpoint in early stage TNBC. The concept for this neoadjuvant setting trial, which will be conducted at a few select U.S. sites, originated from Peregrine’s ongoing collaboration with Memorial Sloan Kettering Cancer Center (MSKCC). The company has filed a study protocol to its existing bavituximab IND application in the U.S. and is currently working to open clinical trial sites, including one that will be led by David B. Page, M.D., at the Providence Cancer Center in Oregon.
As part of the company’s collaboration with AstraZeneca, Peregrine plans to initiate a Phase 1/1b study of bavituximab in combination with durvalumab and chemotherapy in multiple solid tumors in 2016. The Phase 1 part of the trial is designed to confirm the tolerability of the combination of bavituximab and durvalumab and establish a recommended dose regimen for the Phase 1b part of the trial, which will assess the safety and activity of the combination of bavituximab, durvalumab and chemotherapy.
Peregrine recently announced a new research collaboration with NCCN to expand the company’s ongoing clinical research and development of bavituximab for the treatment of a range of tumors. NCCN, a not-for-profit alliance of 26 of the world's leading cancer centers devoted to patient care, research, and education, is dedicated to improving the quality, effectiveness, and efficiency of cancer care so that patients can live better lives. Multiple investigator-initiated clinical and correlative studies with bavituximab in multiple cancers will be initiated at NCCN Member Institutions and their affiliate community hospitals through a $2 million research grant to NCCN’s Oncology Research Program (ORP). NCCN will be responsible for oversight and monitoring of the clinical studies through the research grant. The company expects results from this collaboration to further support the ongoing development of bavituximab as a key component of various combination cancer treatments.
Bavituximab is an investigational chimeric monoclonal antibody that targets phosphatidylserine (PS). Signals from PS inhibit the ability of immune cells to recognize and fight tumors. Bavituximab blocks PS and, in turn, is believed to remove this immunosuppressive signal and send an alternate immune activating signal. PS targeting antibodies have been shown to shift the functions of immune cells in tumors, resulting in robust anti-tumor immune responses.
Peregrine Pharmaceuticals, Inc. is a biopharmaceutical company focused on developing therapeutics to stimulate the body's immune system to fight cancer. Bavituximab, the company's lead immunotherapy candidate, is in late-stage clinical development for the treatment of both lung cancer and breast cancer. The company will also evaluate the combination of bavituximab and durvalumab, AstraZeneca’s investigational anti-PD-L1 immune checkpoint inhibitor, in a range of cancer types under a clinical collaboration.
In addition to its drug development programs, Peregrine also has in-house cGMP manufacturing capabilities through its wholly-owned subsidiary Avid Bioservices, Inc. which provides development and biomanufacturing services for both Peregrine and third-party customers.