MET Inhibitor May Be Effective in Treating Patients With Hepatocellular Carcinoma With MET Overexpression Who Were Not Successful With Nexavar

A 500 mg dose of Tepmetko, a MET inhibitor, in patients with hepatocellular carcinoma who were previously treated with Nexavar led to a 12-week progression-free survival rate of 63.3%.

Tepmetko (tepotinib) was well tolerated and effective at its recommended dose of 500 mg once per day in patients with advanced hepatocellular carcinoma and MET overexpression who were previously treated with Nexavar, according to a study published in the British Journal of Cancer.

“At the (recommended phase 2 dose of 500 mg once per day, Tepmetko) showed promising efficacy and, therefore, a positive benefit-risk balance for patients with (advanced hepatocellular carcinoma) with MET overexpression who had previously received (Nexavar) therapy,” the study authors wrote.

The MET gene is often dysregulated in patient with hepatocellular carcinoma, which can lead to rapid tumor growth and aggressive disease, according to the study’s introduction.

“MET is … a therapeutic target in (hepatocellular carcinoma) after failure of (Nexavar) and probably also after other treatments that target the VEGF pathway,” the study authors wrote.

Tepmetko is a highly selective MET inhibitor that can promote antitumor activity in patients with solid tumors including those with hepatocellular carcinoma.

This study was conducted in two parts. Researchers performed the phase 1b study to determine the recommended dose of Tepmetko to be used for the phase 2 study. In the phase 1b study, 17 patients with advanced hepatocellular carcinoma progression who were previously treated with four or more weeks of Nexavar first received 300 mg once per day of Tepmetko during a 21-day cycle, which increased to 500 mg once per day for the second 21-day cycle.

The phase 2 study included 49 patients with advanced hepatocellular carcinoma progression previously treated with four or more weeks with Nexavar and who had MET overexpression. These patients received the recommended dose of Tepmetko determined by the phase 1b study.

Several factors were assessed in these studies. The phase 1b study focused on dose-limiting toxicities (or side effects that would prevent a dose increase) during the first cycle of treatment, whereas the phase 2 study focused on progression-free survival (the time during and after treatment with no disease progression) after 12 weeks of treatment.

No dose-limiting toxicities occurred in the phase 1b study. Based on that, researchers determined that the recommended dose for the phase 2 study is 500 mg.

In the phase 2 study, 63.3% of patients achieved progression-free survival at 12 weeks, which is greater than what researchers hypothesized. The median time to disease progression was four months.

Of the patients in the phase 2 study, 28.6% experienced severe or life-threatening side effect including lipase increase (indicating pancreatitis; 6.1%) and swelling of hands or lower legs (6.1%).

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