Drug Detail

Information about XL147

Generic Name
IND	XL147
Brand Name (US)
Manufacturer	Exelixis
Drug Type	Kinase inhibitor
Delivery	Oral
Approval Status	Phase 1
Indications
Overall Strategy	Oncogenic Signal Path Based
Strategy	Block KIT Signal Path
Drug Category	PI3K inhibitor

PI3K proteins have been identified in crucial signaling paths of multiple cancers. They can become over-active via a variety of mechanisms including upstream signaling. PI3Ks have recently been identified as active downstream signal points in the c-KIT pathway in GIST. A number of PI3K inhibitors have now entered phase I clinical trials.
Preclinical data presented at the 2007 AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics in October 2007 demonstrate that XL147 is a potent and selective inhibitor of Class I PI3K lipid kinases. In preclinical studies, XL147 blocks PI3K signaling in tumor cells in vitro, and exhibits dose-dependent and sustained inhibition of PI3K signaling in multiple human tumor xenograft models when administered as a single agent. These xenograft models also show a correlation between XL147 pharmacodynamic activity and increased apoptosis, inhibition of tumor cell proliferation, and inhibition of angiogenesis. Administration of XL147 in combination with various targeted and chemotherapeutic agents results in enhanced anti-tumor activity in multiple xenograft models over that observed with the corresponding single agents.


Clinical Data

Interim results of an ongoing phase 1 trial of XL147 were presented at the 2007 AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics in October 2007. In this trial, XL147 is dosed daily for 21 days in a 28-day cycle in patients with metastatic or unresectable solid tumors for which known effective measures do not exist or are no longer effective. As of the time of the presentation, no dose-limiting toxicities or adverse events related to XL147 had been reported and dose escalation was ongoing. Plasma insulin is being evaluated as a potential circulating biomarker of PI3K inhibition, and potential biomarkers in other tissues are also under evaluation.