Bavituximab Oncology PDF Print E-mail

About Bavituximab: An Experimental Immuno-Oncology Candidate

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 is believed to affect PS mediated immunosuppressive signaling by blocking the engagement of PS with its receptors as well as by sending an alternate immune activating signal.   In preclinical studies, PS targeting antibodies have been shown to shift the functions of immune cells in tumors, resulting in multiple signs of immune activation and anti-tumor immune responses.

Bavituximab has been granted Fast Track designation by the U.S. Food and Drug Administration (FDA) for the potential treatment of second-line non-small cell lung cancer (NSCLC).

Bavituximab in Combination Therapy

PS targeting antibodies are unique in their utility as they have demonstrated additive anti-tumor effects in preclinical studies when combined with innovative immunotherapies, allowing for potential treatment enhancements across the continuum of cancer patient care.  As a global checkpoint inhibitor, we believe bavituximab holds potential to complement other checkpoint inhibitors with targets such as PD-1, PD-L1 and CTLA-4.  By inhibiting multiple checkpoints simultaneously, there is greater opportunity to establish an immune reactive environment that recognizes and eliminates cancer cells.  In particular, preclinical studies show that combination treatment with a preclinical bavituximab-equivalent antibody and an anti-PD-1 antibody yields superior tumor growth inhibition in a larger percentage of subjects while also exhibiting multiple immunostimulatory changes associated with anti-tumor immune responses, as compared to anti-PD-1 alone.  Additionally, translational studies utilizing human tumor samples have shown the ability of bavituximab to induce multiple signs of immune activation in tumor samples with low PD-L1 expression, highlighting the potential of bavituximab to convert patients with low PD-L1, who typically do not respond to anti-PD-1 treatment, into responders.

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.

Bavituximab has been granted Fast Track designation by the U.S. Food and Drug Administration (FDA) for the potential treatment of second-line non-small cell lung cancer (NSCLC).

AstraZeneca (AZ) Collaboration

In August 2015, Peregrine and AZ entered into a cancer immunotherapy clinical trial collaboration.  The collaboration will evaluate bavituximab, in combination with AstraZeneca's investigational anti-PD-L1 immune checkpoint inhibitor, durvalumab (MEDI4736).  The planned Phase I/Ib trial will evaluate the safety and efficacy of bavituximab in combination with durvalumab in multiple solid tumors.  The Phase I part of the trial is expected to establish a recommended dose regimen for the combination and the Phase Ib part of the trial will assess the safety and efficacy of the investigational combination. The initial trial will be conducted by Peregrine.

Bavituximab and durvalumab are investigational immunotherapies with different mechanisms that are believed to assist the body's immune system in fighting cancer. Bavituximab targets and modulates the activity of phosphatidylserine (PS), a highly immune-suppressive molecule expressed broadly on the surface of cells in the tumor microenvironment.  In preclinical studies, PS targeting antibodies have demonstrated the ability to increase activated T-cells in tumors and fight cancer by reversing the immunosuppressive environment that many tumors establish in order to proliferate.  MEDI4736 is a monoclonal antibody directed against programmed cell death ligand 1 (PD-L1).  Signals from PD-L1 help tumors avoid detection by the immune system. Preclinical data have demonstrated that combining the enhanced T-cell mediated anti-tumor activity of a PS targeting antibody with antibodies targeting the PD-1/PD-L1 pathway, prolong the ability of tumor-specific T-cells to continue attacking the tumor.

National Comprehensive Cancer Network (NCCN) Collaboration

In January 2016, Peregrine entered into a new research collaboration with the National Comprehensive Cancer Network® (NCCN®) to expand the company's ongoing clinical research and development of bavituximab in combination with novel I-O agents, for the treatment of a range of tumors.  NCCN, a not-for-profit alliance of 27 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.  Peregrine has provided a $2 million research grant to the NCCN’s Oncology Research Program (ORP) to conduct multiple investigator-initiated clinical and correlative studies with bavituximab in a variety of tumor types.  NCCN will be responsible for oversight and monitoring of the clinical studies through the research grant.  It is expected that as many as five different clinical studies will be conducted as part of this collaboration, potentially providing Peregrine with a wealth of valuable human data to inform future development of bavituximab.

Investigator Sponsored Trials (ISTs)

As part of our commitment to develop bavituximab, Peregrine allows for ethical independent clinical research to be conducted by highly-qualified third-party investigators. The value of the scientific research that is produced by such investigators is key to complementing Peregrine-sponsored research helping ensure we better understand the broad potential of bavituximab.  Peregrine has supported multiple  ISTs, each designed to evaluate bavituximab’s potential in the treatment of serious, life-threatening cancers.  Current ISTs include:

  • Phase I Trial:  IST of bavituximab in combination with capecitabine and radiation in patients with advanced rectal cancer: This is a Phase I single-arm, open-label, dose-escalation trial that 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 2 weeks of bavituximab administration by itself. Surgery will follow the last bavituximab administration by 4-8 weeks (i.e., 6-10 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. The unique identifier for this trial on ClinicalTrials.gov is NCT01634685.

SUNRISE Phase III Trial of Bavituximab Launched in Second-Line NSCLC

On February 25, 2016, Peregrine announced the discontinuation of the company's Phase III SUNRISE trial of bavituximab in patients with previously treated locally advanced or metastatic non-squamous non-small cell lung cancer (NSCLC). The decision to modify the status of the trial was based on the recommendation of the study's Independent Data Monitoring Committee (IDMC) following a pre-specified interim analysis performed after 33% of targeted overall events (patient deaths) in the study were reached. The interim analysis results demonstrated that the bavituximab plus docetaxel combination group did not show a sufficient improvement in overall survival as compared to the docetaxel group to warrant continuation of the study. Though the interim analysis showed that the bavituximab combination group performed as expected according to the original trial assumptions in terms of overall survival, the docetaxel group dramatically outperformed overall survival expectations based on the original trial assumptions and as compared to recently published studies.

 

Future Perspectives

 

Looking ahead, the company’s priority is to generate clinical evidence of bavituximab’s ability to improve patient outcomes when combined with immuno-oncology agents. To this end, Peregrine and its collaborative partners are designing an immuno-oncology clinical program that will allow the company to best evaluate the additive anti-tumor effects of bavituximab and  other treatments, including durvalumab.

 

To learn more information about bavituximab’s historical preclinical and clinical data, click here.