A phase 1, open-label, dose escalation study of AMG 337 in Asian patients (pts) with advanced solid tumors.

e13538 Background: In the first-in-human study of AMG 337, an investigational, selective, oral MET kinase inhibitor, in Western pts with advanced solid tumors, headache was the main adverse event (AE); AMG 337 doses up to 300 mg QD were tolerated. This study assessed tolerability and safety, including dose-limiting toxicities (DLTs), of AMG 337 in Asian pts with advanced solid tumors. Methods: Eligible pts were Asian, aged ≥20 years, with ECOG PS ≤2 and pathologically confirmed, advanced solid tumors for which prior Tx for advanced disease was received, no standard Tx exists, or standard Tx was refused. Pts enrolled in a 3+3+3 dose escalation scheme. Two cohorts (AMG 337 150 and 300 mg QD) received AMG 337 orally in 28-day cycles. After all pts in a cohort completed a 28-day safety observation period, a dose-level review meeting was convened to determine whether DLT criteria had been met for dose escalation. Endpoints: AEs and DLTs. Results: As of JUN 18, 2014, cohort 1 (AMG 337 150 mg QD) enrolled 4 Japanese pts (female, n=2; male, n=2) aged 41–70 years with lung, hepatic, cecal, or pancreatic tumors (each n=1); 4 pts were evaluable for safety (3 for DLTs). As of OCT 13, 2014, cohort 2 (AMG 337 300 mg QD) enrolled 7 Japanese pts (female, n=2; male, n=5) aged 45–74 years with bladder, colon, or liver carcinoma (each n=1), gastric (n=2) or rectal adenocarcinoma (n=1), or duodenal neuroendocrine carcinoma (n=1); 7 pts were evaluable for safety (6 for DLTs). No DLTs were observed. All pts experienced AEs. All AEs were grade 1 or 2; headache was the most common (Table). Steady-state Cmaxand AUC mean (±SD) estimates were 3.90 (2.03) mg/L and 36.4 (20.0) mg·h/L, respectively, in cohort 2. The recommended dose of AMG 337 for the currently open phase 2 study is 300 mg QD. Conclusions: The safety profile of AMG 337 in Asian pts with advanced solid tumors was consistent with that observed in Western pts. Further evaluation of AMG 337 in pts with MET-amplified tumors is warranted. ClinicalTrials.gov identifier: NCT02096666. Clinical trial information: NCT02096666.Incidence of AEs. Cohort 1 (n=4) Cohort 2 (n=7) Pts with AEs,* n Any AE 4 7 Headache 2 6 Vomiting 3 4 Decreased appetite 2 4 Nausea 3 2 Dry skin 1 3 Rash 0 3 Malaise 0 2 Diarrhea 1 1 Hypoalbuminemia 1 1 Peripheral edema 1 1 *AEs occurring in ≥2 pts in cohort 1 + 2.