Telisotuzumab Vedotin

Overview

Telisotuzumab vedotin (also known as Teliso‑V; ABBV‑399; US brand name Emrelis, telisotuzumab vedotin‑tllv) is a c‑Met–directed antibody–drug conjugate (ADC) developed by AbbVie. In the United States, it received FDA accelerated approval on May 14, 2025, for adults with previously treated, locally advanced or metastatic, non‑squamous NSCLC with high c‑Met protein overexpression (≥50% of tumor cells with 3+ IHC by an FDA‑approved test). The approval was based on objective response rate (ORR) and duration of response (DOR) from the phase 2 LUMINOSITY trial; a phase 3 confirmatory trial comparing telisotuzumab vedotin with docetaxel is ongoing. (fda.gov)

Mechanism of action

• Target: c‑Met (MET) receptor tyrosine kinase overexpressed in a subset of NSCLC. (ascopubs.org)
• Construct: humanized anti‑c‑Met antibody (telisotuzumab/ABT‑700) linked via a cleavable valine–citrulline (vc) linker to the microtubule‑disrupting payload monomethyl auristatin E (MMAE). Internalization into c‑Met–expressing tumor cells releases MMAE to induce cell‑cycle arrest and apoptosis. Reported average drug‑to‑antibody ratio (DAR) is approximately 3 in preclinical/early reviews of this ADC class. (ascopubs.org)
• Patient selection: Companion diagnostic VENTANA MET (SP44) RxDx Assay approved to identify “high c‑Met” (≥50% tumor cells with 3+ staining) for this indication. (fda.gov)

Efficacy

• Phase 2 (LUMINOSITY; NCT03539536) in previously treated, EGFR–wild‑type, non‑squamous NSCLC with c‑Met overexpression:
• High c‑Met subgroup: ORR 34.6% (95% CI 24.2–46.2); median DOR 9.0 months (95% CI 4.2–13.0). Overall (high + intermediate): ORR 28.6%; median DOR 8.3 months. Dose 1.9 mg/kg IV every 2 weeks. (ascopubs.org)
• The FDA’s approval summary (subset n=84 with high c‑Met) reported ORR 35% (95% CI 24–46) and median DOR 7.2 months (95% CI 4.2–12). (fda.gov)

• Additional analyses presented in 2025 suggested activity across prior‑therapy subgroups (prior platinum, ICI, or both). (onclive.com)

• Earlier clinical experience:

• First‑in‑human phase 1 of telisotuzumab vedotin showed antitumor activity in c‑Met–overexpressing NSCLC and established the ADC’s safety profile. (ascopubs.org)

• Combination studies in EGFR‑mutated, c‑Met–positive NSCLC previously treated with EGFR TKIs:

  • Telisotuzumab vedotin + erlotinib (phase Ib) demonstrated objective responses with manageable toxicity. (ascopubs.org)
  • Telisotuzumab vedotin + osimertinib (phase I/Ib) showed responses post‑osimertinib progression in c‑Met–overexpressing, EGFR‑mutant disease. (pubmed.ncbi.nlm.nih.gov)

• Phase 3 confirmatory trial: TeliMET NSCLC‑01 (NCT04928846) is an open‑label, randomized study of telisotuzumab vedotin vs docetaxel in previously treated, c‑Met–overexpressing, EGFR–wild‑type, non‑squamous NSCLC; primary completion is estimated for 2028. (ascopubs.org)

Safety

Across LUMINOSITY and pooled safety data used for approval, the most common adverse reactions (≥20%) included peripheral neuropathy, fatigue, decreased appetite, and peripheral edema. Laboratory abnormalities (grade 3–4 ≥2%) included decreased lymphocytes, increased glucose, elevated ALT/GGT, and electrolyte abnormalities. Interstitial lung disease and respiratory failure were rare grade 5 TRAEs reported in the ASCO 2024 meeting abstract. Peripheral sensory neuropathy and edema are characteristic toxicities of MMAE‑containing ADCs. (fda.gov)

Ongoing and other investigations

• Phase 2 trial in previously untreated MET‑amplified NSCLC (NCT05513703) is evaluating telisotuzumab vedotin monotherapy (background notes include a retrospective ORR of 80% in a small MET‑amplified subset from prior study). (ascopubs.org)
• Additional subgroup and regional analyses (e.g., Asian cohorts) have been presented, reporting responses consistent with the overall LUMINOSITY population. (iaslc.org)

Further reading

• FDA accelerated approval summary (US, May 14, 2025). (fda.gov)
• LUMINOSITY primary analysis (ASCO 2024 abstract). (ascopubs.org)
• Phase Ib telisotuzumab vedotin + erlotinib (Journal of Clinical Oncology, 2023). (ascopubs.org)
• Phase I/Ib telisotuzumab vedotin + osimertinib after prior osimertinib (PubMed, 2024/2025). (pubmed.ncbi.nlm.nih.gov)
• First‑in‑human phase 1 telisotuzumab vedotin monotherapy (Journal of Clinical Oncology, 2018). (ascopubs.org)
• Phase 3 TeliMET NSCLC‑01 trial synopsis (ASCO 2024 abstract) and current status. (ascopubs.org)

Notes: Continued approval in the United States is contingent upon verification and description of clinical benefit in the ongoing phase 3 trial. Outside of the approved US indication, telisotuzumab vedotin remains investigational. (fda.gov)

Last updated: Oct 2025