Phase I/II study of E7050 (golvantinib) in combination with sorafenib in patients (pts) with advanced hepatocellular carcinoma (HCC): Phase I results.

Abstract

294 Background: Golvatinib (G) is highly potent, small molecule ATP-competitive inhibitor of the c-Met receptor tyrosine kinase and multiple members of the Eph receptor family as well as c-Kit and Ron, based on isolated kinase assays. G plus sorafenib (S) had an additive cell killing effect in a HepG2 hepatocellular cell viability assay, thus warranting further evaluation of the combination in HCC. Methods: The study is an ongoing open-label phase I/II study. Eligible pts have advanced HCC, Child-Pugh (CP) A or B, up to 2 prior regimens, including S. A 3+3 dose escalation design was used to determine the maximum tolerated dose (MTD) with planned doses of G (200 mg, 300 mg, 400 mg) PO qd each in combination with S 400 mg bid in 28 day cycles.The dose limiting toxicity (DLT) evaluation period was the first 28 days. Treatment continued until disease progression or development of unmanageable toxicities. Response was assessed by RECIST 1.1. Phase I is complete and preliminary data are presented. Results: 13 pts (med age: 60; M/F: 83%/17%, CP A/B: 92%/8%) were enrolled in 2 cohorts and the MTD was declared as G 200 mg qd and S 400 mg bid. Median treatment duration, 112 days. Confirmed partial responses (PRs) were observed in 2/12 (17%) pts and durable SD was observed in 4/13 (31%) pts based on investigator assessment. Conclusions: G in combination with S appeared to demonstrate manageable toxicity in advanced HCC pts. The PRs and durable SD observed in this pretreated pt population appear favourable and support continued evaluation in phase II. Clinical trial information: NCT01271504. [Table: see text]