Targeting discloses andrew mccutchen the VEGF dejan kovacevic details receptor has beenrecognized as a potential anti-cancer strategy in multiple tumors. MET amplification has been demonstrated in some NSCLCs.Expression of VEGF has been observed in a variety of cancers and has beenassociated with prognostic significance. More frequently, MET is either over-expressed or activated in theabsence of mutation in glioblastomas, breast carcinomas, some gastric cancers,and other solid tumors. MET is mutationally activated in some tumor types, such ashereditary and sporadic papillary renal cell carcinoma and some head and neckcancers. These biological processescontribute to the transformation, progression, survival, and metastasis ofcancer cells. About XL184XL184 (BMS-907351) is a small molecule designed to inhibit MET, VEGFR2, and RET.MET is a receptor tyrosine kinase that plays a key role in cellularproliferation, migration, and angiogenesis.

Abstract 2048, entitled "Neurovascular imaging in GBM patientsquantifies early physiologic changes after treatment with XL184, an inhibitor ofmultiple receptor tyrosine kinases: results from a Phase 2 study" will bepresented by Gregory Sorensen, MD, from the Massachusetts General Hospital,Boston, MA, and abstract 2049, entitled "Correlative tumor molecular profilingand plasma biomarker analysis in a phase 2 study of XL184 in patients withprogressive or recurrent glioblastoma multiforme" will be presented by SamuelDePrimo, PhD, Exelixis Inc, South San Francisco, CA autographed baseball . Correlative tumor profiling and biomarker evaluation and vascular imaging datafrom this trial will also be presented in two additional posters in the sameposter session forbes field . XL184 will be evaluated at a lower dose of 125 mgdaily in order to provide continuous and sustained exposure to the drug in thispreviously treated glioblastoma population jason kendall . In the study, 87% of patients had a dose interruption of XL184, median averagedaily dose was 122 mg/day mondesi house . Adverse events of special interest were: hypertension(all incidences, 39%; Grade 3/4, 7%), palmar-plantar erythrodysesthesia (30%;7%), bleeding events (28%; 9%), proteinuria (26%; 0%), pulmonary embolism (9%;7%) and craniotomy wound dehiscence (4%; 2%). The most frequently occurring Grade 3 and Grade 4 adverse eventswere: fatigue (30%), alanine aminotransferase increase (9%), confusional state(9%), lipase increase (9%), lymphopenia (9%), convulsion (7%), headache (7%),and hypophosphatemia (7%). The efficacy evaluable population was defined as patients having received atleast 1 dose of XL184 and either had at least 1 post-baseline tumor assessmentper investigator or failed to return for any tumor assessments because of deathor clinical determination of progression.

In an exploratoryanalysis, 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 baseball managers . The median duration ofresponse by IRF was 2.9 months (range = 1.9-8.6 months) mondesi's house . The overall rateof response in all patients, including the refractory population of previouslytreated patients with an antiangiogenic therapy, was 15% nationals baseball tickets . By ITT analysis, 7 of 35 (20%) of theantiangiogenic naïve patients had a confirmed partial response dejan kovacevic .

Tumor response, as determined by an independent radiology facility (IRF), usingMacDonald criteria were reported baseball tickets . Importantly, the trial did notexclude patients previously treated with an antiangiogenic agent forbes field . To date, 46 patients who make up the intent to treat(ITT) population have been enrolled in the trial, including 30 (65%) in firstrelapse and 16 (35%) in second or third relapse jason kendall . The exploratory study is evaluating the safety, tolerability and clinicalactivity of XL184 at a continuous daily dose of 175 mg in patients withpreviously treated GBM . local time on Sunday, May 31, 2009, at the American Society ofClinical Oncology (ASCO) Annual Meeting, which is being held May 29-June 2 inOrlando.