A phase I clinical trial to assess the safety, pharmacokinetics, and antitumor activity of glumetinib (SCC244) in patients with advanced non-small cell lung cancers (NSCLCs).

e21702 Background: Aberrant activation of the MET pathway is associated poor prognosis and poor response to standard therapies in cancer patients. Glumetinib (SCC224) is an oral potent and highly selective MET inhibitor. This is an open label, dose-escalation, phase I clinical study to determine the safety, pharmacokinetics and anti-tumor activity in patients with advanced NSCLC regardless of MET status. Methods: Patients with advanced NSCLC failed standard treatments received glumetinib orally according to one of four dose escalation regimens on a 28-day cycle: 100 mg, 200 mg, 300mg and 400 mg once daily, in a Pharmacologically Guided Dose Escalation (PGDE) design (a variation of the standard 3+3 design). The primary endpoints are the incidence of dose limit toxicity (DLT), maximally tolerated dose (MTD), biologically effective dose (BED). The secondary endpoints are treatment-emergent adverse events (TEAE), safety and tolerability, anti-tumor efficacy, pharmacokinetics, and its metabolites. Results: As of Feb 7, 2020, a total of eighteen eligible (18) patients were enrolled into this study: 3 at 100 mg, 3 at 200 mg, 6 at 300 mg and 6 at 400 mg. Only one patient among 6 evaluable patients at 400mg cohort reported one DLT of grade 3 vomiting. Treatment-related adverse events mostly were grade 1 or 2 nausea, vomiting, elevated alkaline phosphatase, elevated conjugated bilirubin, edema, headache, asthenia and decreased appetite. Non-DLT treatment related G3/4 adverse events were peripheral edema (n = 1, 5.5%), hypothyroidism (n = 1, 5.5%). Absorption was rapid after dosing and the median time to reach maximum plasma drug concentration ( T max ) was 2.0‐6.0 hours. The mean value of half-life(t 1/2 ) in each dose group ranged from 20.43h to 35.36 h. In response to glumetinib, one patient with MET overexpression at 200mg dose level had a best of response of partial response and completed 44 weeks glumetinib treatment, 4 patients (3 with MET amplification) had a best of response of stable disease. Conclusions: Glumetinib was well tolerated at doses up to 400 mg once daily and demonstrated clinical activity in advanced NSCLC with MET alterations. Glumetinib is used in ongoing clinical trials to further explore safety and efficacy in NSCLC. Clinical trial information: NCT03466268.