Reference Detail

Ref Type

Journal Article

PMID

(32328660)

Authors

Shitara K, Yamazaki K, Tsushima T, Naito T, Matsubara N, Watanabe M, Sarholz B, Johne A, Doi T

Title

Phase I trial of the MET inhibitor tepotinib in Japanese patients with solid tumors.

Journal	Vol	Issue	Date	Pages	Journal Short Title
Japanese journal of clinical oncology			2020 Apr 24	859-866	Jpn J Clin Oncol

URL

Abstract Text

Tepotinib (MSC2156119J) is an oral, potent and highly selective small molecule mesenchymal-epithelial transition factor (MET) inhibitor for which the recommended Phase II dose of 500 mg once daily has been defined, based on the first-in-man trial conducted in the USA and Europe. We carried out a multicenter Phase I trial with a classic `3 + 3' design to determine the recommended Phase II dose in Japanese patients with solid tumors (NCT01832506).Patients aged ≥20 years with advanced solid tumors (refractory to standard therapy or for whom no effective standard therapy was available) received tepotinib at 215, 300 or 500 mg once daily in a 21-day cycle. Occurrence of dose-limiting toxicities during cycle 1 was used to determine the maximum tolerated dose. Efficacy, safety and pharmacokinetics were also evaluated to support the dose assessment.Twelve patients were treated. Tepotinib was generally well tolerated with no observed dose-limiting toxicities; treatment-related adverse events were mainly grades 1-2. The tolerability profile of tepotinib was similar to that observed in non-Japanese populations. Pharmacokinetics in Japanese and Western patients was comparable. One patient with gastric cancer and one patient with urachal cancer had stable disease of ≥12 weeks in duration. The observed safety profile and pharmacokinetics are comparable with those in patients from the USA and Europe, and the recommended Phase II dose of tepotinib in Japanese patients was confirmed as 500 mg once daily.These results, including initial signals of antitumor activity, support further development of tepotinib in Japanese patients with cancer.

Filtering

Case insensitive filtering will display rows if any text in any cell matches the filter term
Use simple literal full or partial string matches
Separate multiple filter terms with a space. Any order may be used (i. e. a b c and c b a are equivalent )
Filtering will only apply to rows that are already loaded on the page. Filtering has no impact on query parameters.
Use quotes to match on a longer phrase with spaces (i.e. "mtor c1483f")

Sorting

Generally, the default sort order for tables is set to be first column ascending; however, specific tables may set a different default sort order.
Click on any column header arrows to sort by that column
Hold down the Shift key and click multiple columns to sort by more than one column. Be sure to set ascending or descending order for a given column before moving on to the next column.

Molecular Profile	Treatment Approach

Gene Name	Source	Synonyms	Protein Domains	Gene Description	Gene Role

Therapy Name	Drugs	Efficacy Evidence	Clinical Trials
Tepotinib	Tepotinib	0	6

Drug Name	Trade Name	Synonyms	Drug Classes	Drug Description
Tepotinib	Tepmetko	EMD1214063\|EMD-1214063\|EMD 1214063\|MSC2156119\|MSC-2156119\|MSC2156119J	MET Inhibitor 59	Tepmetko (tepotinib) selectively binds to the proto-oncogene hepatocyte growth factor receptor (HGFR or c-Met), which inhibits c-Met phosphorylation and disrupts c-Met-mediated signaling pathways, thereby suppressing tumor growth in tumor cells with activated or overexpression of c-Met protein (PMID: 32328660). Tepmetko (tepotinib) is FDA approved for use in patients with metastatic non-small cell lung cancer harboring MET exon 14 skipping mutations (FDA.gov).

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