Pfizer Inc. announced the discontinuation of A4021018 (also known as ADVIGO 1018), a phase 3 trial examining the effects of investigational compound figitumumab (CP-751,871) in combination with erlotinib as a second/third-line treatment in patients with previously treated advanced non-adenocarcinoma non-small cell lung cancer (NSCLC). An independent Data Safety Monitoring Committee (DSMC) recommended A4021018 be stopped after concluding that the addition of figitumumab to erlotinib is unlikely to demonstrate a statistically significant improvement in the primary endpoint of overall survival compared to erlotinib alone in the study population.
"This outcome is disappointing to us and to patients with NSCLC. Pfizer is working to thoroughly analyze all available data from the figitumumab program to better understand the compound and the IGF-1R (insulin growth factor-1 receptor) pathway," said Dr. Mace Rothenberg, senior vice president of clinical development and medical affairs for Pfizer's Oncology Business Unit. "As a pioneer in the IGF-1R field, we are committed to a thorough evaluation of figitumumab. We will carefully review our extensive clinical database and use this information to refine the figitumumab clinical program with the goal of identifying the right patient population in which to evaluate this compound."
The company has notified A4021018 clinical investigators and has initiated the notification procedure for all involved regulatory agencies of the discontinuation of A4021018. Investigators have been instructed to work with all of their patients in the A4021018 study on an individual basis to determine an appropriate course of action.
In December 2009, Pfizer announced the stop of A4021016 (ADVIGO 1016), a Phase 3 study examining the effects of figitumumab as first-line treatment in patients with advanced non-adenocarcinoma NSCLC, after an analysis by the DSMC showed that addition of figitumumab to carboplatin plus paclitaxel would be unlikely to meet the primary endpoint of improved overall survival compared to paclitaxel plus carboplatin alone.
Pfizer is continuing to study figitumumab in clinical trials for the potential treatment of prostate, breast and lung cancers, and Ewing's sarcoma.
Figitumumab, an investigational fully human monoclonal antibody, is a highly specific inhibitor of the insulin growth factor-1 receptor (IGF-1R) pathway. The IGF-1R pathway is thought to be one of the fundamental signalling pathways that leads to uncontrolled growth and survival of tumour cells, and may represent a resistance mechanism against EGFR inhibitors and other anti-cancer therapies.