Teliso-V ctDNA Study Finds 100% ORR in KRAS-G12C and Better Survival When Baseline ctDNA Is Low

In the LUMINOSITY stage-2 analysis, 83 previously treated, EGFR-wild-type, c-Met-overexpressing NSCLC patients received telisotuzumab vedotin, an ADC targeting c-MET, 1.9 mg/kg Q2W and had serial 521-gene ctDNA sequencing. About 50% of all NSCLC cases demonstrate an overexpression of c-MET. Overall ORR in this ctDNA-evaluable set matched the parent trial at 28.6% (12/42) for high baseline ctDNA (median mean-VAF ≥ 2.05%) and 28.6% across the full EGFRwt population, but low-ctDNA patients had significantly longer mPFS (8.1 vs 5.4 mo) and mOS (16.3 vs 8.5 mo). Genomically, KRAS alterations were common (24%); strikingly, KRAS G12C tumors posted a 100% ORR (5/5) versus 23% (3/13) for other KRAS variants. Notably, KRAS G12C makes up 13% of NSCLC cases. Week-6 molecular responders (≥50% drop in mean-VAF) showed higher ORR (35%), mPFS (8.5 mo) and mOS (15.5 mo) versus 5.7 mo and 12.2 mo in non-responders. Emerging ctDNA amplifications in ERBB2/FGF/FGFR coincided with later clinical progression, hinting at resistance paths. Standard second-line docetaxel historically yields ORR ≈ 7-24% and mPFS ≈ 3-4 mo.9), underscoring Teliso-V’s advantage, especially in ctDNA-low or KRAS G12C subsets.