What Is C-Met Mutated Non-Small Cell Lung Cancer?
C-Met (also known as MET) encodes the hepatocyte growth factor receptor (HGFR or c-Met), a protein that regulates cell growth, survival, migration, and invasion. Mutations in the c-Met gene, such as exon 14 skipping, can lead to aberrant activation of signaling pathways that promote tumor development and progression in non-small cell lung cancer (NSCLC). These mutations are present in approximately 3–4% of NSCLC cases and are associated with poor prognosis and resistance to standard therapies.
Epidemiology of C-Met Mutated NSCLC
The global incidence of C-Met mutated NSCLC is projected to rise due to increasing awareness and advancements in diagnostic techniques. In 2017, the total number of cases in the 7MM (United States, EU5, and Japan) was approximately 16,658, with Germany reporting the highest incidence among EU5 countries. Japan accounted for about 12% of the total cases in the 7MM. The epidemiology is further segmented into total incident cases, age-specific cases, gender-specific cases, stage-specific cases, type-specific cases, and total treated cases.
Market Trends and Growth Projections
The MET inhibitors market for lung cancer was valued at USD 2.5 billion in 2022 and is expected to reach USD 4.8 billion by 2030, growing at a compound annual growth rate (CAGR) of 8.8% from 2024 to 2030. This growth is driven by the increasing prevalence of lung cancer, advancements in targeted therapies, and the rising demand for personalized medicine. The market is also witnessing a shift towards combination therapies and the development of next-generation MET inhibitors.
Leading Companies in C-Met Mutated NSCLC
Key pharmaceutical companies actively involved in the development and commercialization of therapies for C-Met mutated NSCLC include:
- AstraZeneca: Developed Tagrisso, a leading drug for NSCLC with EGFR mutations. The company is also pursuing approval for Datopotamab deruxtecan, a targeted treatment in collaboration with Daiichi Sankyo. Analysts view both Dato-DXd and another drug, Enhertu, as potentially high-earning.
- Johnson Johnson: Received FDA approval for a chemotherapy-free combination therapy using Rybrevant and lazertinib for NSCLC patients with EGFR mutations. This combination also targets the MET gene. JJ expects over $5 billion in peak sales from Rybrevant and is poised to launch the combination treatment imminently.
- Nuvalent: Developed zidesamtinib and NVL-655, which showed promising efficacy in NSCLC patients with ROS1 and ALK mutations, respectively. Analysts forecast a multibillion-dollar potential for these therapies. Shares of Nuvalent surged after positive trial results demonstrated considerable efficacy in lung cancer patients unresponsive to previous treatments.
- Merck: Offers Tepmetko (tepotinib), an oral MET inhibitor approved in the U.S. and Japan for NSCLC patients with MET exon 14 skipping alterations. Tepotinib first received marketing approval in Japan in March 2020 and in the U.S. in February 2021.
- Novartis: Developed Capmatinib, another MET inhibitor approved for NSCLC patients with MET exon 14 alterations.
- Vebreltinib: An oral MET inhibitor approved in China for NSCLC patients with MET exon 14 skipping mutations. Vebreltinib selectively binds to c-Met, preventing its phosphorylation and thereby disrupting c-Met signal transduction pathways.
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