On 3rd February 2021, the US FDA approved Tepmetko as the First and Only Once-daily Oral MET Inhibitor for Patients with Metastatic NSCLC with METex14 Skipping Alterations. Tepmetko is a product of Merck KGaA.
Mechanism of Action: Tepmetko is an oral MET inhibitor that inhibits the oncogenic MET receptor signaling caused by MET (gene) alterations. It has a highly selective mechanism of action, with the potential to improve outcomes in aggressive tumors that have a poor prognosis and harbor these specific alterations.
Approved Indication: Treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) harboring mesenchymal-epithelial transition (MET) exon 14 skipping alterations. Approved for both treatment naïve and previously treated METex14 positive NSCLC patients. Patients with metastatic NSCLC should be selected for the treatment based on the presence of MET exon 14 skipping alterations.
Unmet Need: Patients with this aggressive lung cancer are often elderly and face a poor clinical prognosis. There is a pressing need for targeted treatments that have the potential to generate durable anti-tumor activity and improve the lives of patients with this challenging disease. The availability of a new precision medicine for NSCLC with METex14 skipping alterations advances patient access to targeted treatment and underscores the importance of routine comprehensive biomarker testing for patients with this challenging cancer.
Target Population: In the US in 2020, there were an estimated 228,820 new cases of lung cancer and more than 135,000 deaths from lung cancer. Alterations of the MET signaling pathway, including MET exon 14 (METex14) skipping alterations, are estimated to occur in 3% to 4% of NSCLC cases.
Clinical Trials: The approval is based on results from the pivotal Phase II VISION study evaluating TEPMETKO as monotherapy in patients with advanced NSCLC with METex14 skipping alterations. In the study, TEPMETKO demonstrated an overall response rate of 43% (95% CI, 32–56) in treatment-naïve patients (n=69) and 43% (95% CI, 33-55) in previously treated patients (n=83). Median duration of response (DOR) was 10.8 months (95% CI, 6.9-NE) and 11.1 months (95% CI, 9.5-18.5) among treatment-naïve and previously treated patients, respectively. Duration of response of six months or more occurred among 67% of treatment-naïve patients and 75% of previously treated patients, and duration of response of nine months or more occurred among 30% of treatment-naïve patients and 50% of previously treated patients. The safety population included 255 patients with NSCLC positive for METex14 skipping alterations, who received TEPMETKO in the VISION study. Fatal adverse reactions occurred in one patient (0.4%) due to pneumonitis, one patient (0.4%) due to hepatic failure, and one patient (0.4%) due to dyspnea from fluid overload. Serious adverse reactions occurred in 45% of patients who received TEPMETKO. Serious adverse reactions occurring in >2% of patients included pleural effusion (7%), pneumonia (5%), edema (3.9%), dyspnea (3.9%), general health deterioration (3.5%), pulmonary embolism (2%), and musculoskeletal pain (2%). The most common adverse reactions (≥20%) in patients who received TEPMETKO were edema, fatigue, nausea, diarrhea, musculoskeletal pain, and dyspnea.
- EMD Serono Inc. https://www.emdgroup.com/en/news/tepotinib-fda-approval-metex14-03-02-2021.html
- TEPMETKO® Prescribing Information. Rockland, MA: EMD Serono Inc.; 2021.
- Global Burden of Disease Cancer Collaboration. Global, regional, and national cancer cadence, mortality, years of life lost, years lived with disability, and disability-adjusted life-years for 29 cancer groups, 1990 to 2017; a systematic analysis for the Global Burden of Disease Study. JAMA Oncol. 2019;5:1749–1768.
- American Cancer Society. Key Statistics for Lung Cancer. American Cancer Society. Atlanta, Ga. 2020. Accessed at https://www.cancer.org/cancer/lung-cancer/about/key-statistics.html.