Merck, known as MSD outside the United States and Canada, has announced positive results from the pivotal phase 3 TroFuse-005 trial evaluating Sacituzumab Tirumotecan (sac-TMT), an investigational TROP2-directed Antibody-Drug Conjugate (ADC) being developed in collaboration with Kelun-Biotech. The study met its dual primary endpoints of overall survival (OS) and Progression-Free Survival (PFS) in patients with advanced or recurrent endometrial cancer who had previously received platinum-based chemotherapy and anti-PD-1/L1 immunotherapy.

According to the company, TroFuse-005 is the first global phase 3 trial to demonstrate significant improvement in both OS and PFS compared to chemotherapy in this patient population, and the first ADC to achieve this outcome in endometrial cancer treatment in the setting studied. The trial also met its key secondary endpoint of objective response rate.

The randomised, open-label, multicentre global study enrolled 776 patients with endometrial carcinoma and carcinosarcoma. Participants received either sac-TMT or physician’s choice chemotherapy consisting of doxorubicin or paclitaxel. At a pre-specified interim analysis, sac-TMT demonstrated statistically significant and clinically meaningful improvements in survival outcomes compared to standard chemotherapy options.

Merck stated that the safety profile of sac-TMT remained consistent with previously reported studies, with no new safety signals identified during the trial. Detailed data from the study will be presented at an upcoming medical meeting and discussed with regulatory authorities worldwide.

Dr. Domenica Lorusso, Global Lead Investigator for the study and professor of Obstetrics and Gynaecology at Humanitas University and Humanitas San Pio X in Milan, said the findings highlight the potential of TROP2-directed ADCs in addressing a major unmet need in advanced endometrial cancer. She noted that patients whose disease progresses after platinum and immunotherapy treatment currently have limited therapeutic options.

Dr. Dean Y Li, President, Merck Research Laboratories, said the positive outcome reinforces the company’s strategy of advancing one of the industry’s broadest ADC pipelines. He added that sac-TMT’s proprietary bifunctional linker technology is designed to maximise payload delivery to tumours while reducing impact on healthy cells, potentially positioning the therapy as a cornerstone treatment in advanced endometrial cancer.

The TroFuse programme currently includes 17 ongoing global phase 3 trials across multiple tumour types, including breast, bladder, cervical, gastric, ovarian and non-small cell lung cancers. Merck said the programme represents the broadest clinical development effort for any TROP2-directed ADC to date, spanning more than 15,000 patients worldwide.

Sac-TMT is an investigational ADC carrying a belotecan-derived topoisomerase I inhibitor payload linked through a bifunctional linker designed to improve tumour targeting and reduce payload loss during circulation. TROP2, the therapy’s target, is highly expressed in several common cancers compared to healthy tissue.

Endometrial cancer is the most common cancer affecting the uterus and one of the few cancers worldwide with rising incidence and mortality rates. In the United States alone, an estimated 68,270 new cases and around 14,450 deaths are projected in 2026. Patients with recurrent or metastatic disease often face poor outcomes, particularly following failure of platinum-based chemotherapy and immunotherapy.

Under an existing collaboration agreement, Kelun-Biotech granted Merck exclusive rights to develop, manufacture and commercialise sac-TMT outside Greater China, including Mainland China, Hong Kong, Macau and Taiwan.