Telisotuzumab Vedotin-tllv Receives Accelerated Approval for High c-Met Non-Squamous NSCLC
Expert Perspectives · Lyn Brook · 2025-05-16
The FDA has granted accelerated approval to telisotuzumab vedotin-tllv (Emrelis™, AbbVie Inc.), a c-Met–directed antibody and microtubule inhibitor conjugate, for the treatment of adults with locally advanced or metastatic, non-squamous non–small cell lung cancer (NSCLC) exhibiting high c-Met protein overexpression. This approval is specifically for patients whose tumors show strong (3+) c-Met staining in at least 50% of cells, as determined by an FDA-approved test, and who have received prior systemic therapy.
In conjunction with this approval, the FDA also authorized the VENTANA MET (SP44) RxDx Assay (Roche Diagnostics) as a companion diagnostic to identify patients with non-squamous NSCLC who may benefit from telisotuzumab vedotin-tllv therapy.
Why This Approval Matters
The accelerated approval of telisotuzumab vedotin-tllv provides a new targeted treatment option for patients with advanced non-squamous NSCLC and high c-Met protein overexpression, a population with limited therapeutic choices after prior systemic therapy. This decision highlights the importance of biomarker-driven therapy in lung cancer and offers hope for improved outcomes in this subset of patients.
LUMINOSITY Study: Efficacy and Safety
Efficacy of telisotuzumab vedotin-tllv was evaluated in the LUMINOSITY study (NCT03539536), a multicenter, open-label, multicohort trial. The study enrolled 84 patients with epidermal growth factor receptor (EGFR) wild-type, non-squamous NSCLC with high c-Met protein overexpression, all of whom had previously received systemic therapy. Patients received telisotuzumab vedotin-tllv at the recommended dose of 1.9 mg/kg, up to a maximum of 190 mg for patients ≥100 kg, as an intravenous infusion every two weeks, continuing until disease progression or unacceptable toxicity.
Primary efficacy end points included confirmed overall response rate (ORR) and duration of response (DOR), both assessed by blinded independent central review (BICR) using RECIST v1.1. The results demonstrated an ORR of 35% and a median DOR of 7.2 months.
Managing Adverse Events
The most common adverse events experienced in ≥20% of patients were peripheral neuropathy, fatigue, decreased appetite, and peripheral edema. The most common grade 3 or 4 laboratory abnormalities experienced in ≥2% of patients were decreased lymphocytes, increased glucose, increased alanine aminotransferase, increased gamma-glutamyl transferase, decreased phosphorus, decreased sodium, decreased hemoglobin, and decreased calcium.
Clinical Implications and Future Outlook
“Telisotuzumab vedotin-tllv was associated with durable responses in c-Met protein-overexpressing nonsquamous EGFR-wildtype NSCLC, especially in those with high c-Met,” concluded D. Ross Camidge, MD, PhD, Professor of Medical Oncology at the University of Colorado Anshutz Medical Campus, and colleagues, in their published results of the LUMINOSITY trial, on which approval was based. “Adverse events were generally manageable.”
Dosing and Administration
The recommended dose of telisotuzumab vedotin-tllv is 1.9 mg/kg, up to a maximum of 190 mg for patients ≥100 kg, administered intravenously every two weeks. Treatment should continue until disease progression or unacceptable toxicity.