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FDA grants accelerated approval to telisotuzumab vedotin for advanced NSCLC with high c-Met overexpression

The U.S. Food and Drug Administration has granted accelerated approval to telisotuzumab vedotin-tllv (Emrelis, AbbVie Inc.), marking a significant milestone in the treatment of advanced non-small cell lung cancer (NSCLC).1

On May 14, 2025, the Food and Drug Administration granted accelerated approval to telisotuzumab vedotin-tllv (Emrelis, AbbVie Inc.), a c-Met-directed antibody and microtubule inhibitor conjugate, for adults with locally advanced or metastatic, NSCLC with high c-Met protein overexpression [≥50% of tumor cells with strong (3+) staining], as determined by an FDA-approved test, who have received a prior systemic therapy. This groundbreaking approval represents the first and only treatment specifically indicated for this challenging patient population, addressing a critical unmet medical need in oncology.

The c-Met protein is a receptor tyrosine kinase that plays a crucial role in cancer progression. c-Met IHC positivity correlates with poor overall survival (OS), which may suggest c-Met’s potential utility as a prognostic biomarker. MET protein overexpression ranges from 15 to 70% in NSCLC, with C-MET protein overexpression also occurs in 25%-75% of NSCLC and is associated with poor prognosis of NSCLC.

Aberrant c-Met signaling contributes to tumor progression, angiogenesis, tumor invasiveness, and metastatic tumor activity, and it is associated with therapeutic resistance and poor prognosis. This makes c-Met an attractive therapeutic target, particularly for patients who have exhausted other treatment options.3

Telisotuzumab vedotin is a c-Met-directed antibody-drug conjugate (ADC) and the first and only treatment approved for this patient population. The drug represents a sophisticated example of precision medicine, combining the targeting specificity of an antibody with the cytotoxic power of chemotherapy.

The FDA’s approval was based on compelling data from the phase 2 LUMINOSITY study (NCT03539536). Efficacy was evaluated in the LUMINOSITY study (NCT03539536), a multicenter, open-label, multi-cohort trial. The trial included 84 patients with epidermal growth factor receptor (EGFR) wild-type, non-squamous NSCLC with high c-Met protein overexpression who had received prior systemic therapy.2

The results demonstrated meaningful clinical activity in this challenging patient population. The major efficacy outcome measures were confirmed overall response rate (ORR) and duration of response (DOR), determined by blinded independent central review (BICR) according to RECIST 1.1. ORR was 35% (95% CI: 24, 46) and median DOR was 7.2 months (95% CI: 4.2, 12).

Prior data reported from LUMINOSITY reported an ORR of 34.6% (95% CI, 24.2%-46.2%) and a median DOR of 9.0 months (95% CI, 4.2-13.0) in patients with non-squamous EGFR-wildtype NSCLC with high c-Met overexpression. Median overall survival (OS) and progression free survival (PFS) were 14.6 months (95% CI, 9.2-25.6) and 5.5 months (95% CI, 4.1-8.3), respectively, for those patients.

In a pooled safety population, the most common adverse reactions (≥20%) were peripheral neuropathy, fatigue, decreased appetite, and peripheral edema. The most common Grade 3 or 4 laboratory abnormalities (≥2%) were decreased lymphocytes, increased glucose, increased alanine aminotransferase, increased gamma glutamyl transferase, decreased phosphorus, decreased sodium, decreased hemoglobin, and decreased calcium.

The most common treatment-related adverse events (TRAEs) of any grade were peripheral neuropathy (30%), peripheral edema (16%), and fatigue (16%). The most common AEs of grade 3 or higher was peripheral neuropathy (7%). These toxicities are manageable with appropriate monitoring and supportive care.

FDA also approved the VENTANA MET (SP44) RxDx Assay (Roche Diagnostics) as a companion diagnostic test to aid in detecting c-Met protein overexpression in patients with non-squamous NSCLC who may be eligible for treatment with Emrelis. This precision diagnostic approach ensures that only patients most likely to benefit from treatment receive the therapy.

The recommended telisotuzumab vedotin-tllv dose is 1.9 mg/kg (up to a maximum of 190 mg for patients ≥100 kg), as an intravenous infusion every 2 weeks, until disease progression or unacceptable toxicity.

Looking ahead, telisotuzumab vedotin is being further evaluated as a monotherapy in patients with previously treated c-Met overexpressing NSCLC in the randomized Phase 3 confirmatory global study TeliMET NSCLC-01. Enrollment in the study is underway and continues across global clinical trial sites.

The accelerated approval of telisotuzumab vedotin represents a transformative advancement for patients with advanced NSCLC and high c-Met protein overexpression. This application was granted priority review and breakthrough designation. As the first targeted therapy for this specific biomarker-defined population, telisotuzumab vedotin exemplifies the potential of precision oncology to deliver meaningful clinical benefits to patients with historically limited treatment options.

The success of telisotuzumab vedotin also highlights the growing importance of antibody-drug conjugates in cancer therapy, offering a sophisticated approach to selectively deliver potent cytotoxic agents directly to tumor cells while minimizing systemic toxicity.

References:

  1. FDA grants accelerated approval to telisotuzumab vedotin-tllv for NSCLC with high c-Met protein overexpression. FDA.gov. May 14, 2025.
  2. Camidge DR, Bar J, Horinouchi H, et al. Telisotuzumab vedotin monotherapy in patients with previously treated c-Met protein-overexpressing advanced nonsquamous EGFR-wildtype non-small cell lung cancer in the phase II LUMINOSITY trial. J Clin Oncol. 2024;42(25):3000-3011.
  3. The Role of MET and c-Met in Advanced NSCLC. Cancer Network. August 16, 2023.