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PHARMACOLOGY REVIEW
Telisotuzumab Vedotin-tlly (Emrelis)
June 30, 2025 4 minutes read
By William Elliott, MD, FACP, and James Chan, PharmD, PhD
The U.S. Food and Drug Administration (FDA) has granted accelerated approval of telisotuzumab vedotin-tilly (Teliso-V), a first-in-class c-mesenchymal-epithelial transition factor (c-Met)-directed antibody and a microtubule inhibitor conjugate for the treatment of locally advanced or metastatic, non-squamous non-small cell lung cancer (NSCLC). Teliso-V, a humanized immunoglobulin G1k (IgG1k) monoclonal antibody, is conjugated to a microtubule inhibitor, monomethyl auristain E (MMAE), which disrupts the microtubule network of actively dividing cells after intracellular cleavage.1 Each monoclonal antibody molecule carries an average of three MMAE molecules. Teliso-V was granted a priority review and breakthrough designation.2
The FDA also approved a companion diagnostic test (VENTANA MET SP44) RxDx Assay to aid in detecting patients with non-squamous NSCLC overexpressing c-Met protein.1 Teliso-V is distributed by AbbVie Inc. as Emrelis.
Indications
Teliso-V is indicated for the treatment of adult patients with locally advanced or metastatic non-squamous NSCLC with high c-Met protein expression (≥ 50% of tumor cells with strong [3+] staining), as determined by an FDA-approved test, who have received a prior systemic therapy.1 The accelerated approval was based on overall response and duration of tumor response (per Response Evaluation Criteria In Solid Tumor [RECIST] scores). Continued approval may be contingent upon verification of clinical benefit in a confirmatory trial.
Dosage
The recommended dosage is 1.9 mg/kg (maximum of 190 mg for patients ≥ 100 kg) administered by intravenous infusion over 30 minutes every two weeks until disease progression or unacceptable toxicity.1 Dosage reduction, modification, or discontinuation is recommended based on the severity of various adverse reactions. These include peripheral neuropathy, pneumonitis, interstitial lung disease, keratitis, peripheral edema, infusion-related reactions, or other adverse events.1 For patients who experience infusion-related reactions, the following premedications are recommended: antihistamine (H1 and H2 receptor blockers [e.g., diphenhydramine, famotidine]), antipyretic (e.g., acetaminophen), and glucocorticoid (e.g., methylprednisolone) administered 30-60 minutes prior to each infusion.1 Teliso-V is available as 20-mg and 100-mg single-dose vials.
Potential Advantages
Teliso-V offers a treatment option for patients with nonsquamous epidermal growth factor receptor (EGFR) wild-type NSCLC overexpressing c-Met protein.3
Potential Disadvantages
Adverse reactions associated with Teliso-V include peripheral neuropathy (51% [Grade 3 in 11%]), ocular surface disorder (such as blurred vision, keratitis, dry eyes [25%]), interstitial lung disease/pneumonitis (10% [Grade 3, 3%]), and infusion-related reactions (3%).1 Other adverse reactions include fatigue, decreased appetite, nausea, constipation, and vomiting. Laboratory changes (> 30%) include increases in glucose, alanine transaminase, gamma glutamyl transferase, aspartate aminotransferase, alkaline phosphatase, and decreases in calcium, phosphate, lymphocytes, and hemoglobin. Teliso-V can cause embryo-toxicity. For females of reproductive potential, effective contraception should be used during treatment and for two months after the last dose.1
Comments
The MET proto-oncogene encodes the c-Met protein and cell surface receptor for hepatocyte growth factor receptors. In NSCLC there is dysregulated c-Met signaling. Telisotuzumab targets c-Met. Its efficacy was evaluated in an open-label, single-arm multi-cohort trial (LUMINOSITY).2,3 Eligible study participants had locally advanced or metastatic NSCLC with c-Met protein overexpression (≥ 50%) with prior systemic therapy (≤ 1 line). The efficacy population (n = 84) all had EGFR wild-type, a median age of 64 years (range 38-83), 75% were male, 61% were white, 68% were former smokers, 13% were current smokers, 74% had an Eastern Cooperative Oncology Group Performance Status of 1, 96% had prior platinum therapy, and 82% had prior immunotherapy. The major efficacy endpoint was overall response rate (ORR) RECIST version 1.1, assessed by computed tomography or magnetic resonance imaging and by a blinded independent central review. Duration of response was an additional efficacy outcome measure. Teliso-V achieved 35% ORR (all partial response) (95% confidence interval, 24% to 46%). The median duration of response was 7.2 months (4.2, 12), 21% ≥ 12 months. The highest ORR was among participants with c-Met protein-overexpression.3
Clinical Implications
NSCLC is the leading cause of cancer-related death worldwide. It may be attributed to functional changes in membrane receptors and intracellular signaling pathways leading to oncogenesis. These include mutations in the EGFR gene, anaplastic lymphoma kinase gene, and MET gene. C-Met alterations include point mutation, amplification, fusion and protein overexpression.4 Prevalence of overexpression is approximately 25% in patients with non-squamous EGFR wild-type NSCLC.3 Teliso-V is the first antibody drug conjugate that specifically targets this genomic alteration. Teliso-V was granted an accelerated approval to target this MET-expressing cancer with poor prognosis. The cost for a single dose for a 70 kg patient (133 mg) is $19,980 (one single-dose 100-mg vial and two single-dose 20-mg vials).
References
- AbbVie Inc. Emrelis prescribing information. Revised May 2025. https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/761384s000lbl.pdf
- U.S. Food and Drug Administration. FDA grants accelerated approval to telisotuzumab vedotin-tllv for NSCLC with high c-Met protein overexpression. May 14, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-telisotuzumab-vedotin-tllv-nsclc-high-c-met-protein-overexpression
- 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.
- Liang H, Wang M. MET oncogene in non-small cell lung cancer: Mechanism of MET dysregulation and agents targeting the HGF/c-Met axis. Onco Targets Ther. 2020;13:2491-2510.
The U.S. Food and Drug Administration has granted accelerated approval of telisotuzumab vedotin-tilly, a first-in-class c-mesenchymal-epithelial transition factor-directed antibody and a microtubule inhibitor conjugate for the treatment of locally advanced or metastatic, non-squamous non-small cell lung cancer.
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