A phase I trial to determine safety and pharmacokinetics of ASLAN002, an oral MET superfamily kinase inhibitor, in patients with advanced or metastatic solid cancers.

Abstract

Background The MET tyrosine kinase and its ligand, hepatocyte growth factor (HGF) also known as scatter factor, are associated with tumourigenesis and metastasis by promotion of scattering, proliferation, angiogenesis, motility and invasion. ASLAN-002 is a potent inhibitor of MET as well as related kinases. A phase I dose escalation study was conducted to determine the safety and pharmacokinetics of ASLAN-002 in patients with advanced cancer. Methods Patients with advanced or metastatic solid tumours, who had progressed on standard therapy or for whom standard therapy was not known, were administered ASLAN-002 orally. The starting dose was 100mg once daily (QD) with subsequent cohorts to receive doses of 200mg QD, 300mg QD, 450mg QD, 600mg QD, 300mg twice daily (BID), 450mg BID, and 600mg BID. Results Forty patients were included across 7 dose cohorts. Cohort 8 (600mg BID) was not opened due to the lack of appreciable pharmacokinetic (PK) differences between 300mg BID and 450mg BID and higher incidences of grade 3 or 4 adverse events (AE) in Cohort 7 (450mg BID). Fifteen patients (37.5%) experienced a grade 3 or 4 AE. The most commonly reported AEs were nausea (55%), fatigue (47.5%) and constipation (30%). One dose limiting toxicity (DLT) of atrial fibrillation was observed with 450mg BID. Conclusions ASLAN-002 is well tolerated at 300mg BID and is the recommended dose for future phase II studies (RP2D). Clinical Trials Registry Number: NCT01721148 .