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Ref Type Journal Article
PMID (26155941)
Authors Hong DS, Rosen P, Lockhart AC, Fu S, Janku F, Kurzrock R, Khan R, Amore B, Caudillo I, Deng H, Hwang YC, Loberg R, Ngarmchamnanrith G, Beaupre DM, Lee P
Title A first-in-human study of AMG 208, an oral MET inhibitor, in adult patients with advanced solid tumors.
Journal Oncotarget
Vol 6
Issue 21
Date 2015 Jul 30
URL
Abstract Text This first-in-human study evaluated AMG 208, a small-molecule MET inhibitor, in patients with advanced solid tumors.Three to nine patients were enrolled into one of seven AMG 208 dose cohorts (25, 50, 100, 150, 200, 300, and 400 mg). Patients received AMG 208 orally on days 1 and days 4-28 once daily. The primary objectives were to evaluate the safety, tolerability, pharmacokinetics, and maximum tolerated dose (MTD) of AMG 208.Fifty-four patients were enrolled. Six dose-limiting toxicities were observed: grade 3 increased aspartate aminotransferase (200 mg), grade 3 thrombocytopenia (200 mg), grade 4 acute myocardial infarction (300 mg), grade 3 prolonged QT (300 mg), and two cases of grade 3 hypertension (400 mg). The MTD was not reached. The most frequent grade ≥3 treatment-related adverse event was anemia (n = 3) followed by hypertension, prolonged QT, and thrombocytopenia (two patients each). AMG 208 exposure increased linearly with dose; mean plasma half-life estimates were 21.4-68.7 hours. One complete response (prostate cancer) and three partial responses (two in prostate cancer, one in kidney cancer) were observed.In this study, AMG 208 had manageable toxicities and showed evidence of antitumor activity, particularly in prostate cancer.

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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
Drug Name Trade Name Synonyms Drug Classes Drug Description
AMG208 AMG-208|AMG 208 MET Inhibitor 52 AMG 208 is a small molecule inhibitor of c-MET, which blocks c-MET activation, resulting in inhibition of downstream signaling and potentially resulting in decreased growth of c-MET expressing tumor cells (PMID: 26155941).
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
Unknown unknown prostate cancer not applicable AMG208 Phase I Actionable In a Phase I trial, AMG208 treatment resulted in complete response in 1 and partial response in 2 patients with prostate cancer (PMID: 26155941; NCT00813384). 26155941
Unknown unknown Advanced Solid Tumor not applicable AMG208 Phase I Actionable In a Phase I trial, AMG208 demonstrated safety and preliminary efficacy, resulted in complete response in 2% (1/43), partial response in 7% (3/43) and stable disease in 65% (28/43) of patients with advanced solid tumors (PMID: 26155941; NCT00813384). 26155941