Telisotuzumab Vedotin

Overview

Telisotuzumab vedotin (Teliso-V; formerly ABBV-399; U.S. brand name Emrelis) is a c-Met–directed antibody–drug conjugate developed for cancers with c-Met protein overexpression. It is no longer exclusively investigational: on May 14, 2025, the FDA granted accelerated approval for adults with previously treated, locally advanced or metastatic nonsquamous non-small-cell lung cancer (NSCLC) whose tumors show high c-Met protein overexpression—defined as strong 3+ staining in at least 50% of tumor cells using an FDA-approved test. Continued approval may depend on confirmation of clinical benefit. (fda.gov)

Mechanism of action

Teliso-V consists of a humanized antibody against c-Met—the cell-surface receptor for hepatocyte growth factor—linked through a protease-cleavable linker to monomethyl auristatin E (MMAE). After binding c-Met–expressing cells, the conjugate is internalized and releases MMAE intracellularly. MMAE disrupts microtubules, causing cell-cycle arrest and apoptotic cell death. (ascopubs.org)

Efficacy

The single-arm phase II LUMINOSITY trial evaluated Teliso-V at 1.9 mg/kg intravenously every two weeks in previously treated, c-Met–overexpressing, EGFR-wild-type nonsquamous NSCLC. In the overall efficacy-evaluable population of 168 patients, the updated objective response rate was 29.2%, with a median response duration of 7.2 months. Response was associated with the degree of c-Met expression: the response rate was 34.5% in c-Met-high disease and 23.8% in c-Met-intermediate disease. (pubmed.ncbi.nlm.nih.gov)

The FDA-approved population comprised 84 patients with high c-Met expression. By blinded independent review, the confirmed response rate was 35% (95% CI, 24%–46%), all partial responses; median response duration was 7.2 months, with 59% of responses lasting at least six months and 21% lasting at least 12 months. Because LUMINOSITY lacked a randomized comparator, effects on survival relative to standard therapy remain uncertain and are being evaluated in confirmatory research. (fda.gov)

Safety

Among 168 LUMINOSITY participants, common adverse reactions included peripheral neuropathy (51%; grade 3, 11%), fatigue (29%), peripheral edema (22%), decreased appetite (22%), blurred vision (15%), pneumonia (13%), keratitis (11%), and interstitial lung disease (ILD)/pneumonitis (10%). Serious adverse reactions occurred in 35%, treatment was permanently discontinued because of adverse reactions in 30%, and fatal adverse reactions occurred in 5%. (accessdata.fda.gov)

Important risks include peripheral neuropathy, potentially fatal ILD/pneumonitis, ocular surface disorders, and infusion-related reactions. ILD/pneumonitis included three fatal cases and led to permanent discontinuation in 7% of patients. Ocular surface disorders occurred in 25%, most often blurred vision, keratitis, or dry eye. (accessdata.fda.gov)

Further reading

• Phase II LUMINOSITY primary analysis — Journal of Clinical Oncology
• Updated LUMINOSITY analysis — PubMed
• First-in-human phase I study — Journal of Clinical Oncology
• FDA accelerated-approval summary
• FDA prescribing information

Last updated: Sep 2026