An evaluation of telisotuzumab vedotin for the treatment of non-squamous non-small cell lung cancer

INTRODUCTION: Advanced non-squamous non-small cell lung cancer (NSCLC) remains associated with substantial mortality despite major advances in targeted therapy and immuno-oncology. c-Met protein overexpression represents a biologically relevant and relatively prevalent phenotype that may define a therapeutically vulnerable population lacking canonical genomic drivers. AREAS COVERED: This review examines the scientific rationale for targeting c-Met protein overexpression and critically evaluates telisotuzumab vedotin (Teliso-V), a c-Met-directed antibody-drug conjugate (ADC) delivering the cytotoxic microtubule polymerization inhibitor MMAE. The structure, mechanism of action, dose optimization strategy, and exposure-toxicity relationships are discussed alongside emerging efficacy data from early-phase studies and the phase II LUMINOSITY trial. The evolving role of biomarker-driven ADC therapy in previously treated EGFR-wildtype non-squamous NSCLC, companion diagnostics, and regulatory considerations are also addressed. EXPERT OPINION: Teliso-V represents an important extension of the ADC paradigm into a protein-expression-defined NSCLC population, demonstrating clinically meaningful activity with a predictable and manageable safety profile dominated by cumulative risk for peripheral neuropathy. While accelerated approval underscores its therapeutic promise, long-term positioning will depend on confirmatory trials, refinement of biomarker testing, and optimization of patient selection. If validated, this strategy may redefine later-line treatment expectations by aligning cytotoxic payload delivery with biologically enriched disease subsets.