Pharma powerhouse Merck has announced a major clinical milestone in endometrial cancer therapy.
Its Phase 3 TroFuse-005 trial of sacituzumab tirumotecan (sac-TMT) has met both primary endpoints—overall survival (OS) and progression-free survival (PFS)—in certain patients with advanced or recurrent endometrial cancer.
The study, evaluating the investigational TROP2-directed antibody-drug conjugate developed with Kelun-Biotech, is the first global Phase 3 trial to show statistically significant improvement in both OS and PFS versus chemotherapy in this patient population.
It also marks the first and only ADC to achieve this outcome in endometrial cancer in this setting.
At a pre-specified interim analysis, sac-TMT demonstrated a statistically significant and clinically meaningful improvement in OS and PFS compared to treatment of physician’s choice in patients who had previously received platinum-based chemotherapy and anti-PD-1/L1 immunotherapy, either together or separately.
The trial also met its key secondary endpoint of objective response rate. Full results will be presented at an upcoming medical meeting and shared with global regulators.
Safety findings remained consistent with earlier studies, with no new safety signals identified.
“These results show sac-TMT may be able to address a critical unmet need for certain patients with advanced endometrial cancer, one of the only cancers increasing in both incidence and mortality worldwide,” said Dr. Domenica Lorusso, the study’s global lead investigator.
“Despite recent advances, patients whose disease progresses following treatment with platinum and immunotherapy are urgently in need of new options, and these findings show for the first time that a TROP2 ADC may be an effective option in this setting.”
Merck Research Laboratories president Dean Y Li called the results a reflection of the company’s broader oncology strategy and ADC pipeline ambitions.
“The scale and ambition of our expansive TroFuse program reflects our deep commitment to advancing one of the industry’s leading ADC pipelines to make a difference for more people facing cancer and builds on our legacy of leadership in gynecologic cancer research,” said Dean Y. Li.
“These findings reinforce our belief that sac-TMT, with its proprietary bifunctional linker designed with the intent to maximize payload delivery to tumors while minimizing impact on healthy cells in the body, has the potential to become a cornerstone in the treatment of certain patients with advanced endometrial cancer."
The TroFuse-005 success also represents the first positive Phase 3 readout in Merck’s broader TroFuse program for sac-TMT.
The program now includes 17 ongoing global Phase 3 trials across multiple tumor types, spanning the widest range of disease settings for any TROP2-directed ADC to date. Ten of these trials focus on women’s cancers.
Merck is evaluating sac-TMT across a broad oncology slate including endometrial, bladder, breast, cervical, gastric, non-small cell lung, and ovarian cancers, in both early and late-stage disease, as monotherapy and in combination with immunotherapies.
