First-in-human (FIH) Phase I Study of GST-HG161, a Potent and Highly Selective C-Met Inhibitor, in Patients with Advanced Solid Tumor.

e16126 Background: GST-HG161 is an orally bioavailable novel potent and highly selective c-Met inhibitor, which displayed significant antitumor activity in preclinical models as well as very desirable pharmaceutical properties for oral dosing. Preclinical studies demonstrated that GST-HG161 has the potential to be effective in HCC patients with active c-Met signaling. Methods: This is an open label, first-in-human, single center, dose-escalation study (NCT04228406) utilizing an accelerated dose escalation design using single patient cohorts for the first two dose levels (60 and 150 mg) followed by a conventional 3+3 design at the 3rd dose cohort (300 mg). Dose escalation is expected to continue to the proposed 7th dose cohort (900 mg). The objective of the study is to determine the maximum tolerated dose and/or recommended Phase II dose, dose limiting toxicities (DLT), safety, pharmacokinetics, pharmacodynamics and preliminary signals of anticancer efficacy of GST-HG161 in patients with advanced solid tumors. Eligible patients are adults with advanced solid tumors refractory to standard therapies with confirmed c-Met positive. The definition of c-Met positive is a) IHC expression of c-Met (positive criteria: 1+ and above) and/or b) FISH amplification of c-Met and/or c) MET exon 14 (METex14) skipping. GST-HG161 is administered orally once-a-day starting on day 1 of each 21 days cycle. Results: To date, 6 patients (CRC 2, Gastric 1, NSCLC 1, HCC 1, Cholangiocarcinoma 1) were enrolled to 3 dose levels (60, 150, and 300 mg). Of these 6 patients, 4 had discontinued GST-HG161 treatment at the data cut-off date of Feb 1, 2020, due to progressive disease (3) and adverse event (1). Two patients at the 300 mg cohort are still on treatment. Overall, 4/6 patients showed no drug-related AEs > Grade 1. One patient reported a DLT: asymptomatic Grade 3 lipase elevation after a single dose of 60mg. To date, no other patients showed elevations of lipase and amylase. Bioanalysis of PK samples from study patients are currently ongoing. PK summary will be reported in the presentation. Conclusions: GST-HG161 has been well tolerated to date in study patients with a manageable safety profile. The dose escalation is expected to continue to the proposed 7th cohort at 900 mg. Clinical trial information: NCT04228406 .