Teliso-V monotherapy and EGFR-TKI combinations in c-Met–over-expressing NSCLC: A systematic review and meta-analysis.

Abstract

e20714 Background: c-Met protein over-expression is frequent in non-small cell lung cancer (NSCLC) and is linked to poor prognosis. Telisotuzumab vedotin (Teliso-V) is an antibody–drug conjugate that targets c-Met overexpression to deliver a cytotoxic payload. We synthesized efficacy for Teliso-V monotherapy and combinations with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). Methods: Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), we searched PubMed, Embase, and major conference proceedings through January 2026 for prospective Teliso-V trials in c-Met–positive advanced NSCLC (immunohistochemistry (IHC) H-score ≥150 or ≥25% 3+ staining). Records were deduplicated, screened, and full texts were assessed, yielding 7 eligible cohorts from 5 prospective trials. Primary outcomes were objective response rate (ORR) and disease control rate (DCR), analyzed separately and stratified by regimen (monotherapy vs combination). Pooled proportions were estimated using random-effects generalized linear mixed models (GLMMs) (random-intercept logistic regression; logit scale). Between-cohort variance (tau-squared) was estimated by maximum likelihood; heterogeneity was summarized using I-squared (I²). Individual cohort confidence intervals (CIs) used Clopper–Pearson; 95% prediction intervals were computed. Results: Monotherapy (k=5 cohorts; N=224) yielded pooled ORR 24.0% (95% confidence interval 16.5–33.6; 95% prediction interval 12.4–41.2) with moderate heterogeneity (I²=52.7%), consistent with clinical and cohort-size differences. Pooled DCR was 60.3% (53.7–66.5) with no observed heterogeneity (I²=0.0%). Combination therapy (k=2 cohorts; N=74) yielded pooled ORR 40.3% (27.7–54.4; 95% prediction interval 24.7–58.3); heterogeneity estimates are imprecise and should be interpreted cautiously because only two combination cohorts were available(I²=65.0%). Pooled DCR was 81.1% (70.6–88.5; 95% prediction interval 70.5–88.5) with low heterogeneity (I²=11.8%). Conclusions: In c-Met–over-expressing advanced NSCLC, Teliso-V shows clinically meaningful activity. Pooled response rates were higher with EGFR tyrosine kinase inhibitor combinations, while disease control was consistent across settings. Findings are limited by single-arm evidence and few combination cohorts and warrant confirmation in larger, controlled studies. Pooled efficacy (percentage). Endpoint & Regimen Cohorts ( k ) Patients ( N ) Pooled Estimate % [95% CI] 95% Prediction Interval Objective Response Rate (ORR) Monotherapy 5 224 24.0 [16.5–33.6] 12.4–41.2 Combination 2 74 40.3 [27.7–54.4] 24.7–58.3 Disease Control Rate (DCR) Monotherapy 5 224 60.3 [53.7–66.5] 53.7–66.5 Combination 2 74 81.1 [70.6–88.5] 70.5–88.5