The fourth domestic MET inhibitor: tepotinib hydrochloride was approved for marketing

Introduction: The fourth domestic targeted drug approved for MET indications (trade name: Tepmetko) is a kinase inhibitor targeting MET. Tepotinib was developed by Merck and was approved by the U.S. Food and Drug Administration (FDA) on February 3, 2021 for the treatment of adult patients with metastatic NSCLC with MET exon 14 skipping mutations.

Mechanism of action

Tepotinib is a powerful drug that effectively regulates the cell cycle by precisely acting on cyclin D1 and p27 proteins, thereby achieving strong inhibition of tumor cell proliferation. Its unique mechanism of action significantly hinders the growth of tumor cells, inducing cell cycle arrest, thereby weakening the tumor's ability to grow. More importantly, tepotinib can also specifically inhibit MET-dependent downstream signaling pathways. This function further strengthens its effect of inhibiting tumor cell proliferation and promotes tumor cell apoptosis.

Usage and Dosage

Tepotinib is an oral drug. The recommended dose is tepotinib 450 mgqd (equivalent to tepotinib hydrochloride 500 mg) until disease progression or intolerable adverse reactions occur. Tepotinib should be swallowed whole and should not be chewed, broken or crushed. The daily medication time should be fixed. If vomiting occurs after taking the medication, the patient is advised to take the next dose within the scheduled time. If the patient experiences adverse reactions, the dose of tepotinib should be reduced to 225 mgqd. If the patient is still unable to tolerate it, the drug should be permanently discontinued.

Therapeutic effect

Compared with chemotherapy, tepotinib combined with gefitinib can significantly improve patients' progression-free survival (PFS), overall survival (OS), objective response rate and response duration. The median PFS in the chemotherapy group was only 4.2 months, while tepotinib combined with gefitinib could be extended to 16.6 months, which was 4 times that of the chemotherapy group! In terms of OS, the median OS of the tepotinib combined with gefitinib group was 37.3 months (only 13.1 months in the chemotherapy group), which means that more than half of the patients can survive for more than 3 years. In terms of safety, the overall safety of tepotinib combined with gefitinib is controllable and can ensure lasting efficacy.