by Dr. C.H. Weaver M.D. 11/2022
On February 3, 2021, the Food and Drug Administration granted accelerated approval to Tepmetko (tepotinib) for adult patients with metastatic non-small cell lung cancer (NSCLC) harboring mesenchymal-epithelial transition (MET) exon 14 skipping alterations.6
Alterations of the MET signaling pathway are found in various cancer types, including 3-5% of individuals with NSCLC. MET mutations correlate with aggressive tumor behavior and poor clinical prognosis.1-3
On February 15, 2024, the Food and Drug Administration granted full approval for the treatment of adult patients with metastatic NSCLC harboring mesenchymal-epithelial transition (MET) exon 14 skipping alterations.
About Tepmetko (tepotinib)
Tepmetko is an oral MET kinase inhibitor that is designed to selectively inhibit the oncogenic signaling caused by MET (gene) alterations, including both MET exon 14 skipping alterations and MET amplifications, or MET protein over expression.4
The initial FDA Breakthrough Therapy Designation was based on data from the ongoing VISION clinical trial (NCT02864992), showing a 50% response rate and an overall response duration of 14 to 17 months in patients with metastatic NSCLC harboring MET exon 14 skipping alterations detected by liquid or tissue biopsy.
Final approval was based on 164 treatment-naïve patients who were reported to have an overall response rate of 57% with 40% of responders having a response duration greater than one year. Among 149 previously treated patients the response rate was 45% with 36% of responders having a greater than 12-month response duration The most common adverse reactions (≥20%) were edema, nausea, fatigue, musculoskeletal pain, diarrhea, dyspnea, decreased appetite, and rash.
The most common side effects reported were edema, fatigue, nausea, diarrhea, musculoskeletal pain, and shortness of breath. Tepotinib can also cause interstitial lung disease, hepatotoxicity, and embryo-fetal toxicity.
Tepotinib is also being investigated in the INSIGHT 2 study (NCT03940703) in combination with the tyrosine kinase inhibitor Tagrisso (osimertinib) in epidermal growth factor receptor (EGFR) mutated, MET amplified, locally advanced or metastatic NSCLC having acquired resistance to prior EGFR TKI.
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References
- Reungwetwattana T, et al. Lung Cancer 2017;103:27-37.
- Mo HN, et al. Chronic Dis Transl Med 2017; 3(3):148-153.
- Lutterbach B, et al. Cancer Res 2007;67:2081–8.
- Bladt, F, et al. Clin Cancer Res 2013;19:2941-2951.
- Paik P, et al. J Clin Oncol 2019;37: (suppl; abstr 9005).
- US Food and Drug Administration. FDA grants accelerated approval to tepotinib for metastatic non-small cell lung cancer. February 3, 2021. http://www.fda.gov/drugs/drug-approvals-and-databases/fda-grants-accelerated-approval-tepotinib-metastatic-non-small-cell-lung-cancer. Accessed February 3, 2021.
