Based on revised data from a troubled phase II trial of the new drug bavituximab, Peregrine Pharmaceuticals is aiming to move the agent into phase III testing in non–small-cell lung cancer (NSCLC) by the end of 2013.
Bavituximab, a first-in-class monoclonal antibody, targets an immunosuppressive molecule called phosphatidylserine; the molecule is usually located inside a cell membrane, but is expressed externally in cells that line tumor blood vessels, making it a potential therapeutic target. Bavituximab is designed to bind to phosphatidylserine and block the immunosuppressive signal, allowing immune systems to fight the tumor.
The phase II trial for the drug as a second-line agent for NSCLC was called into question last September when Peregrine reported some major discrepancies involved with coding of vials. They have since determined that the discrepancies were limited to the placebo and 1 mg/kg dosing arm of the trial, and not the 3 mg/kg arm; to adjust, the company considered the placebo and lower dose patients in one group.
In the new analysis of the 121 patient trial, those patients who received docetaxel(Drug information on docetaxel) plus bavituximab 3 mg/kg had a median overall survival of 11.7 months. Patients in the control group had a median overall survival of 7.3 months, for a hazard ratio of 0.73; the company called this a “meaningful improvement,” but it did not reach statistical significance (P = 0.217). Response rates and progression-free survival also favored the study drug, and there were no significant differences between groups with regard to adverse events.
“These compelling results strongly support advancing the 3 mg/kg bavituximab plus docetaxel combination into phase III development in second-line NSCLC,” said Joseph Shan, vice president of clinical and regulatory affairs at Peregrine, in a press release. The company hopes to initiate a phase III pivotal trial by the end of 2013.
Bavituximab is also being investigated as a first-line agent for NSCLC and for pancreatic cancer, among other indications; the second-line NSCLC use would be the first to make it to phase III trials. In March 2012, Peregrine reported that the study drug in combination with carboplatin(Drug information on carboplatin) and paclitaxel(Drug information on paclitaxel) yielded a median progression-free survival of 5.8 months as a first-line treatment for stage IIIb and stage IV NSCLC, vs 4.6 months with carboplatin and paclitaxel alone. In one other phase I study that is currently recruiting patients, investigators will test bavituximab in combination with pemetrexed(Drug information on pemetrexed) and carboplatin in previously untreated stage IV NSCLC.