The single group, interventional Phase II trial will enroll approximately 36 patients with newly diagnosed glioblastoma. Patients will receive standard of care radiation, as well as daily temozolomide treatment and weekly bavituximab treatment, throughout the 18-week study. The primary objective of the trial is overall survival at twelve months. Secondary outcome measures include progression free survival (PFS) and radiographic response.
“We are hopeful that results from this trial, as well as from the two additional studies at NCCN Member Institutions, will continue to support our belief that bavituximab works to create a more immune active tumor microenvironment in which other therapies are able to have a greater anti-tumor effect,” said Joseph Shan, MPH, vice president, clinical and regulatory affairs of Peregrine. “We look forward to following this important study at the Massachusetts General Hospital Cancer Center, as well as the planned trials at the Moffitt Cancer Center and The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins.”
Results from a previous preclinical study highlighted that PS-targeting antibodies similar to bavituximab synergize with radiation to improve anti-tumor activity in the F98 rat model of glioblastoma. These study data, generated by researchers at the University of Texas, Southwestern, demonstrated that PS-targeting treatment in combination with radiation more than doubled the median survival time of glioma-bearing rats and was significantly superior to either PS-targeting or radiation alone (p < 0.001). Additionally, 13% of the glioma-bearing rats treated with the combination were rendered disease free. These disease-free animals were immune to a rechallenge with F98 glioma cells, suggesting that the combination treatment had induced an adaptive immunity to the tumor cells.
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. Funding for the three investigator-initiated clinical studies has been provided by Peregrine in the form of a research grant to NCCN ORP. NCCN is responsible for oversight and monitoring of the clinical studies through the research grant.
Details of the two additional NCCN-supported studies are as follows:
- A Phase I Trial of Sorafenib and Bavituximab Plus Stereotactic Body Radiation Therapy (SBRT) for 1st Line Treatment of Unresectable Hepatocellular Carcinoma; Jessica Frakes, MD, Moffitt Cancer Center.
- Phase II Study of Pembrolizumab and Bavituximab for Progressive Recurrent/Metastatic Squamous Cell Carcinoma of the Head and Neck; Ranee Mehra, MD, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins.
Bavituximab is an investigational immune-modulatory monoclonal antibody that targets phosphatidylserine (PS), a phospholipid that inhibits the ability of immune cells to recognize and fight tumors. Bavituximab is believed to reverse PS-mediated immunosuppression by blocking the engagement of PS with its receptors, as well as by sending an alternate immune activating signal. 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. This mechanism may play an important role in allowing other cancer therapies to more effectively attack tumors by reversing the immunosuppression that limits the impact of those treatments.
Importantly, bavituximab has also demonstrated a favorable safety and tolerability profile across several clinical trials conducted to date, which may offer the compound a key advantage as the evolving cancer treatment landscape continues to shift to a combination therapy approach. The ability to be added to a range of other cancer therapies without causing added safety concerns may position bavituximab favorably as a component of combination treatments.