A phase I study of E7080 in patients (pts) with advanced malignancies

• DOI: 10.1200/jco.2008.26.15_suppl.3526
• Publication Date: 2017-02-24T07:33:44Z
• Authors: H. Glen; D. R. Boss; R. Morrison; M. Roelvink; J. Wanders; A. Mazur; A. Gupta; A. Das; T. R. Evans; J. H. Schellens
• Keywords: 01 natural sciences; 0104 chemical sciences; 3. Good health

3526 Background: E7080 is a potent inhibitor of the split-kinase family transmembrane growth factor receptors including VEGFRs 1 and 2, also potently inhibits FGFR-1 PDGFR-β tyrosine kinase activities. inhibited VEGF-driven umbilical vein endothelial cell proliferation tube formation in vitro, tumor H460 Colo205 mouse xenografts models vivo at doses 1–100mg/kg. Methods: The primary objective this study was to determine maximum tolerated dose (MTD) limiting toxicity (DLT) pts with advanced solid tumors refractory standard therapies. Eligible were those ECOG PS < 2 adequate haematologic, renal hepatic function. administered orally on once daily continuous schedule 4-week cycles. Dose escalation by an accelerated design (100% increases until 1st pt experienced ≥ grade 2). Samples for pharmacokinetic (PK) analyses collected days 1, 8, 15, 22 29. A food effect PK sub-study ongoing MTD. Results: 59 (35 m, 24 f), median age = 55 yrs (range 25–84) treated levels (mg/day) 0.2, 0.4, 0.8, 1.6, 3.2, 6.4, 12.5, 16, 20, 25 32 mg. Median number cycles 5 (0–22). 53 are evaluable so far. DLTs included 32mg (both proteinuria), each 16mg (hypertension), 12.5mg (proteinuria) 6.4mg (febrile neutropenia). MTD 25mg daily. reductions (n=12pts) most commonly proteinuria (5 pts) hypertension pts). Other 3/4 toxicities include haemorrhage thrombosis (n=1) tachycardia (n=1). 37 now response: have confirmed PR (1 sarcoma, melanoma, carcinoma), had stable disease 16 weeks 8–88). described 2- compartment model. Clearance linear unchanged multiple dosing. saturable decrease distribution volume observed from 0.2 up 1.6 covariate will be reported full presentation. Conclusions: displays safe well signs anti-cancer activity. Author Disclosure Employment or Leadership Consultant Advisory Role Stock Ownership Honoraria Research Expert Testimony Remuneration Eisai Medical