A phase II study of the dual MET/VEGFR2 inhibitor XL880 in patients (pts) with papillary renal carcinoma (PRC)

5103 Background: XL880 is a potent, orally available small molecule inhibitor of MET and VEGFR2/KDR. Activating mutations and/or amplifications in MET have been described in pts with PRC. In a XL880 Phase 1 study with intermittent dosing, 3 of 4 PRC pts had partial responses (PR), two of which are durable for >2 and 1 year respectively. Methods: This is a phase II study enrolling PRC pts stratified based on presence or absence of MET-pathway dysfunction (activating mutation in MET kinase domain, MET [7q31] amplification, or trisomy 7). Pts with PRC, adequate organ function and ECOG 0–2, receive XL880 at 240 mg/day on Days 1–5 of 14 day treatment cycles. Response is assessed every 8 weeks by RECIST criteria. Plasma markers reflecting effects of anti-angiogenic therapy and potential effects of MET inhibition are analyzed. Results: As of 21 Dec 2007, 26 subjects were enrolled (17 germ line MET wildtype, 4 hereditary PRC [HPRC] with a germ line MET mutation, 5 with MET pathway dysfunction). Of 20 evaluable pt...