Abstract Introduction Telisotuzumab Vedotin, an antibody-drug conjugate targeting c-Met overexpression, was approved by the U.S. FDA in May 2025, for previously treated, locally advanced or metastatic non-squamous NSCLC with high c-Met protein expression. This meta-analysis evaluates its comparative efficacy and safety to contextualize its therapeutic role in targeted NSCLC management. Methods A systematic review identified clinical trials of Telisotuzumab Vedotin in c-Met-positive advanced NSCLC. Data on efficacy and safety were pooled using Stata 18.0, applying a random-effects model. Risk of bias was assessed using ROB 2.0 criteria. Results Four clinical studies (n = 168) were analysed, including 126 patients treated with TelisotuzumabVedotin (Teliso-V) and 42 comparators. The pooled objective response rate favoured Teliso-V (OR2.41, 95% CI 1.62-3.58; p 0.001) with higher disease control (OR 1.89, 95% CI 1.30-2.73).Monotherapy studies showed an ORR of 23% (95% CI 14-35), while the phase II LUMINOSITY trial demonstrated 28.6% (95% CI 21.7-36.2) overall and 34.6% (95% CI 24.2-46.2) in c-Met-high tumours. Combination regimens achieved superior efficacy: Teliso-V plus Erlotinib (OR 2.78,95% CI 1.44-5.36; ORR 32.1%) and Teliso-V plus Osimertinib (OR 3.96, 95% CI 2.21-7.08;ORR 50.0%). Progression-free survival improved versus prior therapy (HR 0.64, 95% CI 0.42-0.98; p = 0.04) with longer duration of response (RR 1.48, 95% CI 1.10-2.00). Grade ≥ 3treatment-related adverse events occurred with RR 1.22 (95% CI 0.84-1.76), mainly peripheral neuropathy (RR 1.31, 95% CI 1.01-1.70), anaemia (RR 1.24, 95% CI 0.92-1.66), and fatigue (RR1.10, 95% CI 0.79-1.54); no treatment-related deaths were reported. Conclusion Telisotuzumab Vedotin demonstrates significant efficacy with a favourable safety profile in c-Met-positive advanced NSCLC, supporting its role as a targeted therapeutic option. This abstract is funded by: None
Gunasekaran et al. (2026) studied this question.