NEJM: Efficacy and Safety of Tepotinib in MET Exon 14 Jump Mutation in NSCLC

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 diagnosed each yearMET signaling pathway changes, including MET's Exon Jump mutation No14 and MET amplification, have been found in a variety of types of cancer, including NSCLC, which is associated with aggressive behavior and poor clinical prognosis of tumorsIt is estimated that met signaling pathway changes occur in 3-5% of NSCLC patients
The U.SFood and Drug Administration (FDA) has awarded its target anticancer drug, the oral MET inhibitor tepotinib Breakthrough Drug (BTD), for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) who undergo severity after receiving platinum-containing chemotherapy and carry ingestion-jumping mutation No14 of the MET geneIn March last year, tepotinib was awarded SAKIGAKE (innovative drug) by Japan's Ministry of Health, Labour and Welfare (MHLW) for the treatment of patients with advanced NSCLC who carry the met gene No14 exoon jump mutationIn patients with non-small cell lung cancer (NSCLC), the splicing site mutation resulted in the loss of transcription of the 14th exon in the cancer-causing driver METWe evaluated the efficacy and safety of the highly selective MET inhibitor tepotinib in the patient populationTepotinib is an oral MET kinase inhibitor found within Merck that can be powerful and highly selective lycinter edited by MET (genetically) - including cancer-causing signals caused by MET No14 exomer jump mutation, MET amplification, or MET protein overexpression , with the potential to improve the treatment of prognosis in patients with invasive tumors carrying these specific MET changesIn addition to NSCLC, Merck is also actively evaluating the new treatment of tepotinib for other tumor indicationsTepotinib Molecular Structure (Photo Source: chemicalbook.com) In this open-label phase 2 study, we gave tepotinib (dose 500 mg) to patients with late or metastatic NSCLC who were diagnosed with a met exon 14 jump mutationThe main endpoint was to assess the objective response rate (ORR) by the Independent Data Commission of patients who had been followed for at least 9 monthsThe presence of MET exon 14 jump mutations was also analyzed based on whether the presence of MET exon 14 jump mutations was detected in a liquid biopsy or tissue biopsyAs of 1 January 2020, a total of 152 patients received tepotinib, of which 99 patients were followed up for at least 9 monthsThe ORR assessed by the Independent Data Commission was 46 per cent (the median response duration of the Joint Biopsy Group was 11.1 months)The effective rate of liquid biopsy group was 48%, and the biopsy group was 50%The tissue biopsy group of 60 cases, both methods were positive, the researchers assessed a remission rate of 56%, whether or not receiving late-stage or metastatic disease treatment is similar, are 3 or higher adverse events reported, 28% of patients who were considered to be associated with tepotinib treatment, including 7% peripheral edema; Free DNA was observed at baseline and during treatment in patients with a liquid biopsy sample that corresponded to 67 percent of patientsIn patients with advanced NSCLC who had a diagnosed MET exon 14 jump mutation, the use of tepotinib was associated with partial remission in about half of the patientsPeripheral edema is the main toxic effect of level 3 or higher