- TroFuse-005 randomized 776 patients and met dual primary endpoints (OS and PFS) at a pre-specified interim analysis.
- Investigational sacituzumab tirumotecan (sac-TMT), a TROP2-directed ADC with a belotecan-derived topoisomerase I payload and bifunctional linker, outperformed physician's choice (doxorubicin or paclitaxel) and met the key secondary endpoint (ORR).
- Dosing: sac-TMT 4 mg/kg IV Day 1 every 2 weeks; doxorubicin 60 mg/m² Day 1 q3w; paclitaxel 80 mg/m² Days 1, 8, 15 q4w.
- Merck develops sac-TMT with Kelun-Biotech and holds exclusive rights outside Greater China; the TroFuse program comprises 17 global Phase 3 trials enrolling over 15,000 patients across multiple tumor types.
Key results
At a pre-specified interim analysis, the Phase 3 TroFuse-005 trial (n=776) showed sacituzumab tirumotecan (sac-TMT) produced statistically significant, clinically meaningful improvements in overall survival (OS) and progression-free survival (PFS) versus physician’s choice (doxorubicin or paclitaxel) in patients with advanced or recurrent endometrial cancer after prior platinum chemotherapy and anti‑PD‑1/PD‑L1 therapy; objective response rate was a key secondary endpoint and was met.
Trial design and dosing
TroFuse-005 was a randomized, active-controlled, open-label global Phase 3 (NCT06132958) in endometrial carcinoma and carcinosarcoma; sac-TMT was dosed 4 mg/kg IV Day 1 every 2 weeks, doxorubicin 60 mg/m² Day 1 q3w, and paclitaxel 80 mg/m² Days 1, 8, 15 q4w.
Safety and mechanism
The safety profile was consistent with prior sac-TMT studies with no new signals observed; sac-TMT is a TROP2-directed antibody–drug conjugate carrying a belotecan-derived topoisomerase I inhibitor via a bifunctional linker designed to maximize tumor payload delivery and limit systemic payload loss.
Program scope and collaboration
The TroFuse program comprises 17 ongoing global Phase 3 trials across multiple tumor types and includes more than 15,000 patients worldwide; sac-TMT was developed by Kelun-Biotech, with Merck holding exclusive rights outside Greater China.
