New Treatment for c-MET-Positive Lung Cancer: Telisotuzumab Vedotin Receives FDA Approval

The First FDA Approval Directly Targeting “High c-MET Protein Expression”

On May 14, 2025, the US Food and Drug Administration (FDA) approved telisotuzumab vedotin-tllv (brand name Emrelis, AbbVie Inc.), an antibody–drug conjugate, for patients with non-small cell lung cancer (NSCLC) showing high c-MET protein expression under its accelerated approval program.

These patients must have previously received systemic treatment, and have locally advanced or metastatic nonsquamous NSCLC .

This represents a major development for patients with an NSCLC biological subtype associated with the previously untargeted c-MET protein , because it marks the first approval of an antibody–microtubule inhibitor conjugate for this group.

The Importance of c-MET Expression in Non-Small Cell Lung Cancer

The c-MET (mesenchymal-epithelial transition) receptor is a receptor tyrosine kinase regulating cell growth, survival, migration, and angiogenesis. Normally involved in tissue healing, this protein may, in some cancers, be overexpressed or carry structurally activating mutations.

What Is c-MET Expression Like in NSCLC?

• Approximately 25-30% of patients with NSCLC show c-MET expression.

• “High c-MET expression” is defined as strong (3+) immunohistochemical (IHC) staining in more than 50% of tumor cells .

• When c-MET is overexpressed, tumor cells may become more invasive, metastatic, and treatment-resistant .

Detection: Companion Diagnostic Approval

Alongside this approval, the FDA also approved VENTANA MET (SP44) RxDx Assay , an IHC test, on the same day. It will be used to determine the level of c-MET protein expression and identify patients eligible for Emrelis.

Emrelis (Telisotuzumab Vedotin): How Does It Work?

Telisotuzumab vedotin combines a monoclonal antibody directed against the c-MET receptor with a microtubule inhibitor (MMAE) to form an antibody–drug conjugate (ADC).

The conjugate has two main mechanisms of action:

1. It binds to c-MET and selectively enters the cell.

2. Once inside the cell, the attached MMAE is released and disrupts microtubule polymerization, causing apoptosis (programmed cell death) in the tumor cell .

This targets only cells with high c-MET expression and affects healthy tissues less.

FDA Approval Based on LUMINOSITY

The FDA approval is based on data from LUMINOSITY . This multicenter, open-label trial evaluated patients with:

• EGFR wild-type, nonsquamous NSCLC,

• high c-MET expression,

• and previous systemic treatment;
  84 patients were assessed.

Main Results:

• Objective response rate (ORR): 35% (95% CI: 24–46)

• Duration of response (DOR): median 7.2 months (95% CI: 4.2–12)

These findings are considered clinically meaningful, particularly given the limited treatment options for this subgroup.

Adverse Reactions and Safety Profile

The most common adverse reactions in the pooled safety analysis were:

• Peripheral neuropathy

• Fatigue

• Loss of appetite

• Peripheral edema

Grade 3–4 laboratory abnormalities included lymphocytopenia, hyperglycemia, increased transaminases, decreased phosphate, and hyponatremia.

Dose and Administration

• Dose: 1.9 mg/kg (maximum 190 mg)

• Administration: IV infusion every 2 weeks

• Treatment duration: Until disease progression or intolerable toxicity.

Has It Received FDA Approval Before?

This is the first FDA approval for telisotuzumab vedotin. The drug is also being investigated in other indications, such as liver and gastric cancers, particularly for targeting c-MET-positive tumors.

c-MET-Targeted Treatments

For lung cancer with high c-MET protein, there have already been FDA-approved treatments, but they generally target genetic alterations such as MET gene amplification or MET exon 14 skipping mutations . The first FDA approval directly targeting “high c-MET protein expression”was granted on May 14, 2025, for telisotuzumab vedotin (Emrelis) .

Previous FDA Approvals: MET-Targeted Treatments

1. Capmatinib (Tabrecta)

   • FDA approval: May 2020

   • Indication: MET exon 14 skipping mutation-positive NSCLC

   • Note: Targets the genetic mutation rather than c-MET protein expression.

2. Tepotinib (Tepmetko)

   • FDA approval: February 2021 (accelerated approval)

   • Indication: Advanced NSCLC with a MET exon 14 skipping mutation

   • Note: Likewise selects patients by mutation rather than protein expression.

3. Crizotinib (Xalkori)

   • FDA approval: Has limited use for MET amplification; its main approvals are for ROS1 and ALK.

   • Note: Some studies have evaluated MET-amplified disease, but there is no specific FDA approval in this setting.

In summary:

• Telisotuzumab vedotin (Emrelis), for NSCLC with high c-MET protein expression (more than 50% of cells showing 3+ IHC staining), is the first approved treatment.
• Previous approvals focused on MET genetic alterations (mutation or amplification) , rather than protein overexpression.

Conclusion and Clinical Significance

This approval is important because it expands options for the high-c-MET-expression NSCLC subgroup.
This targeted agent offers patients who have previously received systemic treatment with limited success through conventional approaches, a personalized treatment strategy paired with a precise diagnostic test .