MET targeting

MET signaling is critical in normal biological processes. It activates downstream signaling pathways, including RAS/ERK/MAPK, PI3K/AKT, and JAK/STAT, which drive cell proliferation, motility, and apoptosis. Dysregulation of the MET pathway (for example, MET mutations and amplifications) can drive cancer cell proliferation, survival, invasion, and metastasis.1

Tepotinib – MET kinase inhibitor

Description and Mechanism of Action:

Tepotinib is a small molecule inhibitor of the MET receptor tyrosine kinase. Alterations of the MET signaling pathway are found in various cancer types and are thought to correlate with aggressive tumor behavior and poor clinical prognosis.1,2

In vitro, tepotinib inhibited tumor cell proliferation, anchorage-independent growth, and migration of MET-dependent tumor cells. In mice implanted with tumor cell lines with oncogenic activation of MET, including METex14 skipping alterations, tepotinib inhibited tumor growth, led to sustained inhibition of MET phosphorylation, and, in one model, decreased the formation of metastases.2


Areas of Interest:

  • Non-small cell lung cancer


VISION3 (NCT02864992)

A Phase II single-arm trial to investigate tepotinib in advanced (locally advanced or metastatic) non-small cell lung cancer with MET exon 14 skipping alterations or MET amplification.

INSIGHT 24 (NCT03940703)

A Phase II clinical trial to investigate tepotinib combined with osimertinib in patients with osimertinib-resistant, MET-amplified, EGFR-mutant NSCLC.

Please see full Prescribing Information.


Investigational compounds are not approved by any health authority. Safety and efficacy have not been established.

AKT, protein kinase B; c-Cbl, c-terminal casitas B-lineage lymphoma; CEACAM5, carcinoembryonic antigen-related cell adhesion molecule 5; EGFR/MUC1, epidermal growth factor receptor/mucin 1; ERK, extracellular signal regulated kinase; HGF, hepatocyte growth factor; IAP, inhibitor of apoptosis; JAK, Janus kinase; MAPK, mitogen-activated protein kinase; MET, mesenchymal epithelial transition factor; METex14, MET exon 14; PI3K, phosphatidylinositol 3 kinase; RAS, rat sarcoma; STAT, signal transducers and activators of transcription.


  1. Wu Y-L, Soo RA, Locatelli G, Stammberger U, Scagliotti G, Park K. Does c-Met remain a rational target for therapy in patients with EGFR TKI-resistant non-small cell lung cancer? Cancer Treat Rev. 2017;61:70-81.
  2. TEPMETKO. Prescribing information. Merck KGaA; 2021.
  3. Tepotinib phase II in NSCLC harboring MET alterations (VISION). ClincalTrials.gov identifier: NCT02864992. Updated October 7, 2022. Accessed April 28, 2023. https://www.clinicaltrials.gov/ct2/show/NCT02864992
  4. A study of tepotinib plus osimertinib in osimertinib relapsed MET amplified NSCLC (INSIGHT 2). ClincalTrials.gov identifier: NCT03940703. Updated December 20, 2022. Accessed April 28, 2023. https://www.clinicaltrials.gov/ct2/show/NCT03940703