OSI-930

This drug is manufactured by Astellas pharmaceuticals. It inhibits vascular endothelial growth factor receptors (VEGFR — also known as KDR) and KIT, as well as PDGFRbeta.

A phase I trial of OSI-930 is open at two USA sites (MA and CO) and one site in the United Kingdom. As this is a Phase I trial, there may be stops and starts in patient accrual.

Link to the trial description at clinicaltrials.gov

At the June 2008 ASCO meeting the following papers were presented about OSI-930 (click titles to link to the abstracts).

• A phase I, dose escalation (DE), pharmacokinetic (PK), and pharmacodynamic (PD) study of two schedules of OSI-930, an oral tyrosine kinase inhibitor (TKI), in patients (pts) with advanced solid tumors. 2008 ASCO Annual Meeting Abstract 3553
• Antitumor efficacy of OSI-930 and the molecular targeted agent erlotinib in preclinical xenograft models. 2008 ASCO Annual Meeting Abstract 14596

In a press release following the 2005 meeting of AACR, OSI Pharmaceuticals stated:
“Mary Srebernak et al (abstract #677) presented data on OSI-930, a co-inhibitor of the receptor-tyrosine kinases c-kit and VEGFR (also known as KDR). OSI-930 is equally active against both the mutant and wild type versions of c-kit. OSI-930 was found to have single agent in vivo activity against tumor xenografts that may be driven by wild type c-kit or mutant c-kit. Scientists also characterized the pre-clinical anti-tumor activity of OSI-930 in combination with the chemotherapeutics agents, cisplatin/ etoposide in small cell lung cancer and FOLFOX in colorectal carcinoma. The data demonstrated that OSI-930 can be administered safely and effectively with current standard therapeutic regimens in pre-clinical models and suggest the potential for use of OSI-930 in combination with chemotherapeutics or as maintenance therapy. Combining the inhibition of c-kit originated growth and survival pathways with anti-angiogenic activity arising from VEGFR inhibition in one molecule may potentially translate into a broad range of clinical activity. Data were also presented from several pre-clinical studies designed to identify potential biomarkers of OSI-930 activity. This work used a variety of cell lines that express either mutant or wild type c-kit to determine the effects of OSI-930 treatment on signaling events within cells both in vitro and in vivo. Initial data suggest that the activation state of proteins within the PI-3 kinase signaling pathway may be good biomarkers of OSI-930 activity both in vitro and in vivo. The goal of ongoing studies will be to establish biomarkers suitable to monitor the activity of OSI-930 in clinical trials.”

The most detailed information available at present comes from a January 2006 paper by Garton et al (link to PubMed abstract). In cell studies OSI-930 inhibited multiple activation states of KIT. It is ATP-competitive. It inhibits both wild and mutant KIT, as well as PDGFRbeta. In animal models it induced tumor regressions.

For a PubMed search of papers dealing with OSI-930 click here.