Exelixis, Inc. (Nasdaq:EXEL) today reported interim data from an ongoing phase 1 dose-escalation trial of XL147 (SAR245408) in combination with the EGFR inhibitor erlotinib in patients with advanced solid tumors. XL147 is a selective, orally available small molecule inhibitor of phosphoinositide-3-kinase (PI3K). Activation of the PI3K pathway is a frequent event in human tumors, promoting cell proliferation, survival, and resistance to chemotherapy and radiotherapy. The pathway also has been implicated as a mediator of resistance to epidermal growth factor receptor (EGFR) inhibitors. Neil Faulkner, MD from the Karmanos Cancer Institute, Wayne State University, Detroit, MI, an investigator on the phase 1 trial, will present the data in a poster session (Abstract #C197) beginning at 12:30 pm, local time, on Wednesday, November 18, 2009, at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics, which is being held November 15-19 in Boston. XL147 is being developed with sanofi-aventis.
“The PI3K signaling pathway is frequently dysregulated in a broad spectrum of human tumors, and we believe that XL147 has substantial potential for treating diverse cancers,” said Michael M. Morrissey, Ph.D., president of research and development at Exelixis. “We chose to evaluate XL147 in combination with erlotinib given the data suggesting that PI3K may play a role in resistance to EGFR inhibitors. The results of this phase 1 study thus far are encouraging, and preliminary data demonstrate that the combination regimen simultaneously inhibits PI3K and EGFR signaling. In collaboration with sanofi-aventis, we will continue to evaluate XL147 alone and in combination with a variety of other therapies, with a goal to provide cancer patients and oncologists with new therapeutic options that may overcome resistance mechanisms in cancer.”
The study is evaluating escalating doses of XL147, administered daily for 21 days of a 28-day cycle, in combination with erlotinib, administered daily. As of October 6, 2009, 21 patients with advanced solid tumors had been enrolled in the trial. Tumor types include non-small cell lung cancer (NSCLC) (8), colorectal cancer (5), hepatocellular carcinoma, head and neck squamous cell carcinoma, biliary tract, carcinoid, ethmoid, esophageal, kidney and adenoid cystic cancer (1 each). Patients have been treated at 7 dose levels up to 600 mg XL147/150 mg erlotinib, and the maximum tolerated dose has not yet been reached.