Exelixis, Inc. (Nasdaq:EXEL) and Bristol-Myers Squibb Company (NYSE:BMY) today reported encouraging data from an ongoing phase 2 trial of XL184 in patients with previously treated glioblastoma multiforme (GBM) (study XL184-201).

XL184 is an orally administered small molecule inhibitor of receptor tyrosine kinases including MET, VEGFR2, and RET. Overexpression of MET and VEGFR2, as well as the ligands which activate these receptors, has been shown to correlate with poor prognosis in GBM, which is the most common and aggressive form of brain tumor. In addition, phosphorylated RET has been described in some cases of GBM.

Exelixis is co-developing XL184 with Bristol-Myers Squibb Company. John De Groot, MD, of The MD Anderson Cancer Center, and an investigator on the Phase 2 GBM trial, will present the data in a poster session (Abstract #2047) from 8 a.m. to 12 p.m. local time on Sunday, May 31, 2009, at the American Society of Clinical Oncology (ASCO) Annual Meeting, which is being held May 29-June 2 in Orlando.

The exploratory study is evaluating the safety, tolerability and clinical activity of XL184 at a continuous daily dose of 175 mg in patients with previously treated GBM. To date, 46 patients who make up the intent to treat (ITT) population have been enrolled in the trial, including 30 (65%) in first relapse and 16 (35%) in second or third relapse. Importantly, the trial did not exclude patients previously treated with an antiangiogenic agent.

Tumor response, as determined by an independent radiology facility (IRF), using MacDonald criteria were reported. By ITT analysis, 7 of 35 (20%) of the antiangiogenic naïve patients had a confirmed partial response. The overall rate of response in all patients, including the refractory population of previously treated patients with an antiangiogenic therapy, was 15%. The median duration of response by IRF was 2.9 months (range = 1.9-8.6 months). In an exploratory analysis, among 35 patients with at least one post baseline MRI scan, 12 (34%) had tumor shrinkage ≥50% as their best response as determined by investigator, including 1 patient who had received prior antiangiogenic therapy.

The efficacy evaluable population was defined as patients having received at least 1 dose of XL184 and either had at least 1 post-baseline tumor assessment per investigator or failed to return for any tumor assessments because of death or clinical determination of progression. In the anti-angiogenic naïve population, 7 of 31 (23%) of efficacy evaluable patients had a confirmed partial response by IRF. The 6-month progression-free survival (PFS) rate in patients receiving no prior antiangiogenic therapy was 23%, with 10 patients censored for PFS at the time of analysis, and the median PFS interval was 3.6 months.

“These initial data from our ongoing GBM program are encouraging, and suggest that XL184 could have utility in this underserved indication,” said Michael M. Morrissey, Ph.D., president of research and development at Exelixis.