Merck KGaA recently announced that Japan ’s Ministry of Health, Labour and Welfare (MHLW) has approved its targeted anticancer drug, the oral MET inhibitor Tepmetko (tepotinib), for the treatment of MET gene exon 14 (METex14) jumping Patients with altered unresectable, advanced, or relapsed non-small cell lung cancer (NSCLC). In terms of medication, Tepmekto 500mg daily (2 tablets 250mg).
It is worth mentioning that Tepmetko is the world's first approved oral MET inhibitor for the treatment of advanced NSCLC patients with MET gene changes. In Japan, Tepmetko was previously granted the orphan drug qualification (ODD) and SAKIGAKE qualification (innovative drug).
This approval is based on data from the ongoing single-arm phase II VISION study (NCT02864992). The study enrolled 99 NSCLC patients (including 15 Japanese patients) with METex14 jump changes. The results showed that the liquid biopsy (LBx) or tissue biopsy (TBx) test was confirmed to be carried according to the evaluation of the Independent Review Committee (IRC). Among NSCLC patients with METex14 jumping changes, the objective response rate (ORR) of Tepmetko treatment was 42.4% (95% CI: 32.5, 52.8); among patients identified by LBx and TBx, the median duration of response (DOR) was 12.4 Months (patients identified by LBx [95% CI: 8.4 months, not assessable]; patients identified by TBx [95% CI: 9.7 months, not assessable]).
In a safety analysis of 130 patients, Tepmetko was well tolerated. The most common adverse events (TEAE) during treatment were peripheral edema (53.8%), nausea (23.8%) and diarrhea (20.8%). TRAE resulted in permanent discontinuation in 11 patients (8.5%).
Belén Garijo, CEO and member of the Executive Board of Merck, said: "With the approval of Tepmetko, we are pleased to provide the first approved MET inhibitor in Japan, which will provide a new option to change the METex14 carrying change The treatment process of NSCLC. Tepmetko's companion diagnosis focuses on identifying these genetic changes in patients with non-small cell lung cancer in a flexible and precise manner, while providing liquid and tissue biopsy detection capabilities to best support this targeting The medicine is provided to patients who may benefit. "
tepotinib molecular structure formula (Image source: chemicalbook.com)
Globally, lung cancer is the most common type of cancer and the leading cause of cancer death, with 2 million cases diagnosed and 1.7 million deaths each year. At present, in many types of cancer, three MET signaling pathway changes (including METex14 jump changes, MET amplification, and MET protein overexpression) have been found, which is related to tumor aggressive behavior and poor clinical prognosis. It is estimated that changes in the MET signaling pathway occur in 3-5% of NSCLC cases.
Tepotinib is an oral MET kinase inhibitor found inside Merck, which can potently and highly selectively inhibit carcinogenic signals caused by MET (gene) changes-including METex14 jump changes, MET amplification, and MET protein overexpression- , Has the potential to improve the treatment prognosis of patients with aggressive tumors carrying these specific MET changes. In addition to NSCLC, Merck is also actively evaluating tepotinib combined with new therapies to treat other tumor indications.
In September 2019, the US FDA granted Tepotinib Breakthrough Drug Qualification (BTD) for the treatment of patients with metastatic NSCLC who progressed after receiving platinum-containing chemotherapy and carried METex14 jump changes. Merck plans to submit a new drug application (NDA) for tepotinib to the FDA in 2020.
Currently, Merck is also conducting another study, INSIGHT 2 (NCT03940703), to evaluate the combination of tepotinib and tyrosine kinase inhibitor (TKI) osimertinib for EGFR mutations, METs with acquired resistance to previously accepted EGFR TKI Patients with enlarged, locally advanced, or metastatic NSCLC.