Telisotuzumab vedotin: The first-in-class c-Met-targeted antibody-drug conjugate granted FDA accelerated approval for treatment of non-squamous non-small cell lung cancer (NSCLC)

Abstract

Telisotuzumab vedotin represents a clinically important antibody-drug conjugate (ADC) that received accelerated approval from the US Food and Drug Administration in May 2025, establishing it as the first-in-class targeted therapy for adult patients with immunohistochemistry (IHC)-confirmed high-c-Met, EGFR wild-type, locally advanced or metastatic non-squamous non-small cell lung cancer (NSCLC). Its mechanism of action relies on precise targeting of the c-Met protein receptor, followed by internalization and release of the potent cytotoxic payload monomethyl auristatin E (MMAE) to eradicate tumor cells. The pivotal phase II LUMINOSITY trial demonstrated that the high c-Met overexpressing group had an overall response rate (ORR) of 34.6%. This therapeutic agent addresses a critical unmet need within a molecularly defined NSCLC subpopulation, marking a substantial advancement in c-Met-targeted oncology. The regulatory authorization and clinical use of telisotuzumab vedotin may significantly advance precision medicine for NSCLC, though an ongoing phase III trial will further confirm its efficacy and safety and determine its eligibility for full regulatory approval in the future.