Following its Breakthrough Therapy Designation in December 2021, telisotuzumab vedotin-tllv has cleared another major regulatory hurdle and received accelerated approval from the US Food and Drug Administration (FDA) in May 2025.
The approval makes telisotuzumab vedotin-tllv the first therapy approved for previously treated advanced non-small cell lung cancer (NSCLC) with high c-Met expression. The decision is based on findings from the LUMINOSITY trial.
LUMINOSITY Trial Results
The latest findings revealed that treatment with telisotuzumab vedotin-tllv yielded a 35% overall response rate (ORR) and a median duration of response (DOR) of 7.2 months in participants with high c-Met overexpression.1
Decreased appetite, peripheral edema, fatigue, and peripheral neuropathy were the most common adverse reactions, occurring in at least 20% of participants.1 The most common grade 3 or 4 laboratory abnormalities included:
- Increased glucose
- Decreased sodium
- Decreased calcium
- Decreased hemoglobin
- Decreased phosphorus
- Decreased lymphocyte
- Increased alanine aminotransferase
- Increased gamma glutamyl transferase1
The LUMINOSITY Trial: Design and Outcomes Measured
The ongoing phase II LUMINOSITY trial aims to identify the optimal population of patients with c-Met overexpression in NSCLC who are most likely to benefit from telisotuzumab vedotin-tllv therapy in the second- or third-line setting (Stage 1). The study will expand the group(s) to further evaluate efficacy in the selected population(s) (Stage 2).2
An additional cohort at an alternate dose level will evaluate the safety and efficacy of telisotuzumab vedotin-tllv (Stage 3) after global enrollment for Stage 2 is complete.2
ORR is the primary outcome measure for Stages 1 and 2. The secondary outcomes include DOR, as well as disease control rate (DCR), progression-free survival (PFS), and overall survival (OS).2
The primary endpoint for the alternate dose cohort—or Stage 3—is the number of participants with adverse events.2
About Telisotuzumab Vedotin-tllv
Telisotuzumab is a first-in-class antibody drug conjugate (ADC) that is designed to target c-Met expressing tumor cells using a c-Met binding antibody, a cleavable linker, and monomethyl auristatin E (MMAE).1
Overexpression of c-Met is linked to poor prognosis and occurs in about 25% of advanced, EGFR wild-type, non-squamous NSCLC cases.1
Telisotuzumab vedotin-tllv is AbbVie’s first internally developed solid tumor therapy to receive FDA approval in lung cancer. It represents a potential paradigm shift for this patient population who have historically had limited treatment options.1
Future Directions in High c-Met NSCLC
The phase III TeliMET NSCLC-01 trial is currently evaluating telisotuzumab vedotin-tllv as monotherapy in patients with previously treated c-Met-overexpressed NSCLC.1 Enrollment for the global trial is underway as of May 2025.
Additionally, the FDA approved a novel companion diagnostic, the VENTANA MET (SP44) RxDx Assay, to assess c-Met protein expression in patients with NSCLC.3 This marks the first immunohistochemistry diagnostic companion to identify patients who are eligible for treatment with telisotuzumab vedotin-tllv.1
References
- 1. https://news.abbvie.com/2025-05-14-U-S-FDA-Approves-EMRELIS-TM-telisotuzumab-vedotin-tllv-for-Adults-With-Previously-Treated-Advanced-Non-Small-Cell-Lung-Cancer-NSCLC-With-High-c-Met-Protein-Overexpression
- 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. doi:10.1200/JCO.24.00720
- 3. https://diagnostics.roche.com/us/en/news-listing/2025/roche-receives-fda-approval-for-the-ventana-met-sp44-rxdx-assay-as-the-first-companion-diagnostic-to-identify-non-small-cell-lung-cancer-patients-eligible-for-treatment-with-emrelis.html
