Bavituximab, Peregrine Pharmaceuticals’ lead clinical immunotherapeutic candidate, received Fast Track designation from the FDA to kick off 2014. It’s just the latest milestone in this product’s clinical development as a potential treatment for second-line non-small cell lung cancer (NSCLC). Peregrine’s pipeline also includes the brain cancer agent, Cotara, a tumor necrosis therapy (TNT) that has demonstrated promising results in a phase II clinical trial in patients with glioblastoma multiforme (GBM) who have relapsed.
This past December, Peregrine opened enrollment for the pivotal phase III SUNRISE trial examining bavituximab in the second-line NSCLC setting. The trial is open to patients with stage IIIb/IV nonsquamous NSCLC who have progressed after standard frontline treatment. Patients will be randomized to 1 of 2 treatment arms. All patients will receive up to six 21-day cycles of docetaxel (75 mg/ m2) plus weekly infusions of either bavituximab (3 mg/ kg) or placebo, until progression or toxicity. The primary endpoint of the trial will be overall survival. This trial will enroll approximately 600 patients from more than 100 medical centers worldwide.
Bavituximab is a monoclonal antibody that targets phosphatidylserine (PS), a phospholipid usually found on the inner-leaflet (the cytosolic side) of cell membranes. The phospholipid is highly immunosuppressive, so much so that when it is flipped and is exposed on the outside of tumor cells and cells that line tumor blood vessels, it evades immune detection. Cancer therapies increase PS exposure on the cell surface, further increasing immune suppression in the tumor environment. Bavituximab targets PS and blocks this immunosuppressive signal, and has been shown to reactivate the body’s immune system, restoring its ability to recognize and respond to tumors.
Tumor Necrosis Therapy
The TNT agent Cotara targets necrotic cells found at the core of solid tumors. It works by transporting and binding radioactive iodine to the center of the tumor, allowing the radiation to destroy the tumor from the inside out.
Interim data from a phase II trial involving 41 patients with recurrent GBM showed a median overall survival of 9.3 months. Additionally, 73% of patients were alive at 6 months, 38% at 12 months, and 19% at 24 months. Two patients had survived 3 years after a single treatment with Cotara. Patient treatment in this trial was completed and top-line data were presented in a poster session at the 2011 ASCO Annual Meeting.
With these results in hand, Peregrine approached the FDA in December 2012 with a design for a single registration trial of Cotara in patients with recurrent GBM. The FDA agreed with the proposed randomized trial design comparing two dose levels of Cotara in up to 300 patients. The company will consult with other regulatory agencies because it plans to implement the trial as part of a global registration study.
Peregrine is conducting preclinical research involving I-124 PGN650, which combines the first-in-class PS-targeting F(ab’)2 fully human monoclonal antibody fragment (PGN650) with the PET imaging radioisotope iodine-124. Under an FDA Investigational New Drug application, the company has launched an open-label, single-arm tumor imaging and dosimetry study. In the study, a single intravenous dose of I-124 PGN650 will be administered to up to 12 patients with various solid tumors. Researchers will evaluate radiation dosimetry in critical and noncritical organs, tumor imaging, and safety.
*Filed under exploratory FDA Investigational New Drug application.