About c-Met

High prevalence

c-Met (MET) protein can also be known as HGFR receptor

Approximately
1 in 6, or 14%-17%
of patients with EGFR wt NSq NSCLC, have high c-Met protein overexpression (3+, ≥50%)1,2*

High c-Met protein overexpression (3+, ≥50%) is one of the top 3 most prevalent actionable biomarkers in EGFR wt NSq NSCLC1-8

Prevalence of select biomarkers within EGFR wt† NSq NSCLC patients

Biomarker prevalence is based on data from various sources and patient populations, and does not indicate clinical importance, impact, safety, or efficacy of associated therapies. Some patients may have more than one NSCLC biomarker. Some biomarkers are more established than others.

High c-Met protein overexpression (3+, ≥50%) is distinct from other MET biomarkers (MET gene amplification and METex14 skipping mutation)

Different testing methodologies:

  • High c-Met protein overexpression
    (3+, ≥50%)—MET IHC18
  • METex14 skipping—NGS and
    RT-PCR19
  • MET gene amplification#—NGS
    and FISH19

Patients with high c-Met protein overexpression (3+, ≥50%) can only be detected with MET IHC20

High c-Met protein overexpressed (3+, ≥50%) EGFR wt NSq NSCLC patients (N=72) within a US-based, real-world, retrospective multicenter study2

 

  • In a US-based, real-world, retrospective multicenter study, more than 87% (63 out of 72) of EGFR wt, NSq NSCLC patients with high c-Met protein overexpression (3+, ≥50%) by IHC didn’t have overlap with METex14 skipping or MET gene amplification

    •  

    Based on a single, retrospective, real-world, multicenter study in the US by CARIS Life Sciences, including 417 EGFR wt patients. 72 patients showed high c-Met protein overexpression (3+, ≥50%); among these, 63 patients did not have a concurrent MET gene alteration (MET gene amplification or METex14 skipping) as identified by whole exome sequencing. 2 patients had concurrent MET gene amplification, and 7 patients had concurrent METex14 skipping mutations.

    Of 19 patients identified with either MET gene amplification or METex14 skipping mutations, 10 did not show high c-Met protein overexpression (3+, ≥50%).

*≥50% of tumor cells with strong (3+) c-Met (MET) staining.

†KRAS mutations (KRAS G12C and KRAS non-G12C), BRAF, and METex14 skipping mutations are generally considered mutually exclusive from actionable EGFR mutations with rare co-occurrence often associated to resistance to TKIs.6,17,21,22

‡Prevalence reported for MET gene amplification is representative of De Novo MET gene amplification and may include EGFR mutated patients. MET gene amplification may be evaluated at different molecular thresholds with different testing methods.

§Evidence defining the prevalence of HER2 IHC3+ within EGFR wt NSQ NSCLC is currently limited; range provided includes study populations with EGFR mutations.14,15

Non-actionable biomarker defined as not having an associated FDA-approved indication.

#MET gene amplification is a non-actionable biomarker and may be evaluated at different molecular thresholds with different testing methods.

DNA=deoxyribonucleic acid; EGFR=epidermal growth factor receptor; mRNA=messenger ribonucleic acid; wt=wild-type.

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