Global pharmaceutical company Merck & Co. has announced positive pivotal Phase 3 results for sacituzumab tirumotecan (sac-TMT), an investigational TROP2-directed antibody-drug conjugate (ADC), in patients with advanced or recurrent endometrial cancer who had exhausted prior standard treatment options. The findings from the TroFuse-005 trial mark a potentially significant development in the treatment landscape of a disease with limited therapeutic options after chemotherapy and immunotherapy failure.
According to the company, the global Phase 3 TroFuse-005 study met its primary endpoints of overall survival (OS) and progression-free survival (PFS) in certain patients with advanced or recurrent endometrial cancer. The trial evaluated sac-TMT against treatment of physician’s choice, consisting of chemotherapy agents doxorubicin or paclitaxel, in patients who had previously received platinum-based chemotherapy and anti-PD-1/L1 immunotherapy, administered either sequentially or together.
Merck said the interim analysis demonstrated statistically significant and clinically meaningful improvements in both OS and PFS for patients treated with sac-TMT compared to chemotherapy. In addition to meeting its primary goals, the study also achieved a key secondary endpoint of objective response rate, reinforcing the therapy’s anti-cancer activity in this hard-to-treat patient population.
The company highlighted that TroFuse-005 is the first global Phase 3 trial to demonstrate statistically significant gains in both overall survival and progression-free survival versus chemotherapy in this treatment setting for endometrial cancer. It is also the first and only antibody-drug conjugate to report such efficacy in patients with recurrent or advanced disease following platinum and immunotherapy treatment.
“The results show sac-TMT may address a critical unmet need for patients with advanced endometrial cancer, one of the few cancers increasing in both incidence and mortality globally,” said Domenica Lorusso, global lead investigator of the study and professor of Obstetrics and Gynecology at Humanitas University. She noted that patients whose disease progresses after platinum-based chemotherapy and immunotherapy urgently require additional treatment options.
Merck Research Laboratories President Dean Y. Li said the findings reinforce confidence in sac-TMT’s proprietary bifunctional linker technology, designed to maximize payload delivery to tumors while limiting damage to healthy tissues. He added that the company views the therapy as a potential cornerstone treatment for certain patients with advanced endometrial cancer.
The safety profile of sac-TMT remained consistent with previously reported studies, with Merck reporting no new safety concerns during the trial.
Sac-TMT is being developed through a collaboration between Merck and Sichuan Kelun-Biotech Biopharmaceutical Co., Ltd.. The positive findings also represent the first successful Phase 3 outcome from Merck’s broader TroFuse clinical development program, which currently includes 17 ongoing global Phase 3 studies spanning multiple tumor types.
The TroFuse program is investigating sac-TMT across cancers including endometrial, bladder, breast, cervical, gastric, ovarian, and non-small cell lung cancer, with ten late-stage studies focused on women’s cancers. Among them is the ongoing TroFuse-033 trial evaluating the drug in first-line mismatch repair proficient endometrial cancer.
Merck said detailed data from TroFuse-005 will be presented at an upcoming medical meeting and shared with regulatory authorities globally as the company evaluates future approval pathways for the therapy.