Merck’s sacituzumab tirumotecan (sac-TMT) improved overall and progression-free survival in the Phase 3 TroFuse-005 trial for advanced or recurrent endometrial cancer after platinum chemotherapy and anti-PD-1/L1 therapy, marking the first global Phase 3 success for a TROP2-directed ADC in this setting.
Written By: Chikkula Pavan Kumar, PharmD
Reviewed By: Pharmacally Editorial Team
Merck announced that the Phase 3 TroFuse‑005 trial (NCT06132958) of sacituzumab tirumotecan (sac‑TMT), a TROP2‑directed antibody‑drug conjugate (ADC) developed with Kelun‑Biotech, met its primary endpoints of overall survival (OS) and progression‑free survival (PFS) in patients with advanced or recurrent endometrial cancer whose disease had progressed after platinum‑based chemotherapy and anti‑PD‑1/L1 immunotherapy.
This is the first global Phase 3 study to demonstrate statistically significant improvements in both OS and PFS with a TROP2‑directed ADC compared with chemotherapy in this setting, underscoring sac‑TMT’s potential as a new targeted option for patients with limited therapeutic alternatives.
Phase 3 TroFuse‑005 Trial Results
TroFuse‑005 was a randomized, active‑controlled, open‑label, multicenter trial enrolling 776 patients who had previously received platinum‑based chemotherapy and anti‑PD‑1/L1 immunotherapy, administered either sequentially or in combination. Patients were randomized to receive sac‑TMT or treatment of physician’s choice, consisting of doxorubicin or paclitaxel. At a pre‑specified interim analysis, sac‑TMT demonstrated statistically significant and clinically meaningful improvements in OS and PFS compared with chemotherapy.
Median OS and PFS values, along with hazard ratios, will be presented at an upcoming medical congress. The trial also achieved its key secondary endpoint of objective response rate (ORR), with sac‑TMT showing higher response rates than the comparator arms. Merck reported that the safety profile was consistent with earlier studies, with no new safety signals identified.
“These results show sac‑TMT may address a critical unmet need for patients with advanced endometrial cancer whose disease progresses after chemotherapy and immunotherapy,” said Domenica Lorusso, the study’s global lead investigator emphasizing the poor outcomes and limited treatment options faced by this population.
Dean Y. Li, President of Merck Research Laboratories, added that sac‑TMT’s proprietary bifunctional linker technology is designed to maximize payload delivery to tumor cells while minimizing exposure to healthy tissues, reinforcing Merck’s commitment to advancing innovative ADC therapies for difficult‑to‑treat cancers.
About Sacituzumab Tirumotecan
Sacituzumab tirumotecan is composed of a humanized anti‑TROP2 monoclonal antibody linked to a belotecan‑derived topoisomerase I inhibitor payload through a proprietary bifunctional linker. This design enhances targeted payload delivery to tumor cells while reducing premature release during circulation.
TroFuse‑005 represents the first positive Phase 3 result from Merck’s broader TroFuse clinical development program, which includes 17 ongoing global Phase 3 trials across multiple tumor types. Sac‑TMT is among the lead late‑stage oncology assets being advanced under Merck’s collaboration with Kelun‑Biotech, focused on next‑generation ADC therapies.
If approved, sac‑TMT could provide a new targeted therapeutic option for previously treated advanced endometrial cancer, complementing recent ADC advances in gynecologic oncology such as mirvetuximab soravtansine in ovarian cancer.
Merck plans to present detailed efficacy and safety data at a forthcoming medical congress and share findings with regulatory authorities worldwide, supporting potential global submissions.
About Endometrial Cancer
Endometrial cancer, the most common form of uterine cancer, often progresses after frontline chemotherapy and immunotherapy, leaving patients with few effective treatment options and poor long‑term outcomes.
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About the Writer
Chikkula Pavan Kumar (LinkedIn), PharmD is a Doctor of Pharmacy with a keen interest in clinical pharmacy, pharmacovigilance, and evidence-based practice. In his words, he is passionate about patient safety and translating complex medical information into clear, research-driven communication.