Tisotumab vedotin (tissue factor ADC) triplet with pembrolizumab + carbo pushes 65.8% ORR (1L r/mCC) but with heavy discontinuations

Tisotumab vedotin (TV) is a tissue factor–directed antibody–drug conjugate delivering MMAE; in innovaTV 205/ENGOT-cx8/GOG-3024 (Phase 1b/2; NCT03786081), TV was combined with carboplatin (arm D, 1L; n=33) or pembrolizumab (arm E, 1L; n=33; arm F, 2L+; n=35), and in arm H (1L; n=38) TV + carboplatin + pembrolizumab ± bevacizumab. With data cutoff October 15, 2025, confirmed ORR/median DOR were 54.5%/8.6 mo (D), 40.6%/NR (E), 35.3%/18.2 mo (F), and 65.8%/13.3 mo (H); median PFS was 6.9, 5.3, 5.6, and 10.6 months and median OS was 25.5, 30.7, 15.3, and 28.0 months, respectively—benchmarked against current 1L SOC pembrolizumab + platinum/taxane ± bevacizumab in PD-L1 CPS≥1 (KEYNOTE-826) with ORR ~68%, mPFS 10.4 mo, and updated mOS 28.6 mo. Grade ≥3 treatment-related AEs occurred in 72.7% (D), 45.5% (E), 48.6% (F), and 86.8% (H), and TV discontinuation rates were notable at 24.2%, 24.2%, 34.3%, and 55.3% (H), raising practical tolerability questions even with “no new safety signals” reported.