Sac-TMT Significantly Improves PFS/OS in Pretreated Endometrial Cancer

Sacituzumab tirumotecan (sac-TMT) has become the first TROP2 antibody-drug conjugate (ADC) to demonstrate a statistically significant and clinically meaningful improvement in both overall survival (OS) and progression-free survival (PFS) for patients with advanced or recurrent endometrial cancer, according to a press release from the developer, Merck.¹

The improvement specifically came when compared with treatment of physician’s choice, consisting of doxorubicin or paclitaxel, among those who received prior platinum-based chemotherapy and anti–PD-(L)1 immunotherapy. Sac-TMT also met the key secondary end point of overall response rate (ORR). Regarding safety, findings were consistent with observations in previous studies, with no new safety signals observed.

These findings came from the randomized, global phase 3 TroFuse-005 trial (NCT06132958), which evaluated sac-TMT monotherapy vs treatment of physician’s choice among the aforementioned endometrial cancer population. Reportedly, these data are going to be shared at an upcoming medical meeting and discussed with global regulatory authorities.

“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,” stated Domenica Lorusso, MD, PhD, the study’s global lead investigator, lead investigator for ENGOT and professor of Obstetrics and Gynecology at Humanitas University and Humanitas San Pio X, Milan, in the press release.¹ “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.”

A total of 776 patients were enrolled in TroFuse-005 and randomly assigned to either the experimental or control arm. In the experimental arm, sac-TMT was administered at 4 mg/kg on day 1 of every 2-week treatment cycle. In the control arm, patients received doxorubicin at 60 mg/m² on day 1 of each 3-week cycle and paclitaxel at 80 mg/m² on days 1, 8, and 15 of each 4-week cycle.

The primary end points of the trial were PFS by blinded independent central review and OS. ORR was a key secondary end point; other secondary end points were duration of response and incidence of adverse events, among others.

Eligible patients had a histologically confirmed diagnosis of endometrial carcinoma or carcinosarcoma that is radiographically evaluable, either measurable or nonmeasurable disease per RECIST v1.1, and prior receipt of platinum-based chemotherapy and anti–PD-(L)1 therapy, either separately or together.²

Exclusion criteria included more than 3 prior lines of therapy for endometrial sarcoma, prior treatment with single-agent nonplatinum-based chemotherapy in the third-line setting, prior treatment with a TROP2-targeted ADC, and active inflammatory bowel disease requiring immunosuppressive medication or previous history of inflammatory bowel disease.

“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 [with] cancer and builds on our legacy of leadership in gynecologic cancer research,” Dean Y. Li, MD, PhD, president of Merck Research Laboratories, said in the press release.¹ “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. We thank the patients and investigators for participating in our studies as well as our collaborators at Kelun-Biotech for helping us advance this important treatment.”

References

1. Merck announces TroFuse-005 trial evaluating sacituzumab tirumotecan (Sac-TMT) met primary endpoints of overall survival (OS) and progression-free survival (PFS) in certain patients with advanced or recurrent endometrial cancer. News release. Merck. May 18, 2026. Accessed May 18, 2026. https://tinyurl.com/3sz3xcdw
2. Sacituzumab tirumotecan (MK-2870) in post platinum and post immunotherapy endometrial cancer (MK-2870-005) (TroFuse-005). ClinicalTrials.gov. Updated April 3, 2026. Accessed May 18, 2026. https://tinyurl.com/3ambuun5