Merck and Kelun’s Sac-TMT Extends Survival by Nearly 7 Months in Pretreated Endometrial Cancer

Sacituzumab tirumotecan (sac-TMT), a TROP2-directed antibody-drug conjugate (ADC) developed by Kelun-Biotech and Merck, reduced the risk of death by 32% compared with chemotherapy in patients with advanced or recurrent endometrial cancer previously treated with platinum-based chemotherapy and anti-PD-1 or PD-L1 immunotherapy, according to full results from the Phase 3 TroFuse-005 trial.¹ The data were presented in a Presidential Symposium at the European Society for Medical Oncology (ESMO) Congress 2026 and published simultaneously in The Lancet.^1,2

“The incidence and mortality rates of endometrial cancer are increasing worldwide, and the results from TroFuse-005 have the potential to change the way we treat patients who have received prior platinum-based chemotherapy and anti-PD-1/L1 immunotherapy,” said Domenica Lorusso, MD, PhD, global lead investigator and professor of obstetrics and gynecology at Humanitas University and Humanitas San Pio X in Milan.¹

An estimated 68,270 new cases of uterine cancer and 14,450 deaths are expected in the US in 2026, and death rates have risen about 1.3% per year over the past decade.³ Five-year relative survival is 19.9% for patients whose disease has spread to distant sites.³

How does sac-TMT work?

Sac-TMT pairs an antibody targeting TROP2, a protein expressed on the surface of many solid tumors, with a belotecan-derived topoisomerase I inhibitor payload.¹ According to Merck, the ADC uses a bifunctional linker designed to maximize payload delivery to tumor cells while minimizing payload loss in circulation.¹

Kelun-Biotech developed sac-TMT, and Merck has held exclusive rights outside Greater China since a 2022 partnership.^1,4 The ADC has received four approvals in China since November 2024, in breast and non-small cell lung cancers.⁴ It would compete with two TROP2-directed ADCs already marketed in the US, Gilead’s sacituzumab govitecan (Trodelvy) and AstraZeneca and Daiichi Sankyo’s datopotamab deruxtecan (Datroway).⁴

What did TroFuse-005 show?

The randomized, open-label trial (NCT06132958) enrolled 776 patients at more than 200 centers in 29 countries, with 386 assigned to sac-TMT 4 mg/kg every two weeks and 390 to physician’s choice of doxorubicin or paclitaxel.^1,2,5 Overall survival (OS) and progression-free survival (PFS) were dual primary endpoints.¹

At a median follow-up of 14.0 months, median OS was 19.0 months with sac-TMT vs 12.1 months with chemotherapy (hazard ratio [HR], 0.68; 95% CI, 0.55-0.84; P<.0001).¹ Median PFS was 7.2 months vs 3.9 months (HR, 0.59; 95% CI, 0.50-0.70; P<.0001).¹ The objective response rate was 35.1% vs 17.3%, and median duration of response was 11.1 months vs 6.9 months.¹ Merck first reported in May that the trial met both primary endpoints.⁶

Bhavana Pothuri, MD, MS, a principal investigator and professor of obstetrics and gynecology at NYU Grossman School of Medicine, said the results should establish sac-TMT as a new standard treatment in recurrent endometrial cancer and that clinical guidelines will need to be reassessed.²

What was the safety profile?

Grade 3 or higher treatment-related adverse events occurred in 54.4% of patients receiving sac-TMT and 41.4% receiving chemotherapy.¹ The most common were anemia (23.7%), neutropenia (20.1%), and oral mucositis or stomatitis (9.9%).¹ Discontinuations due to treatment-related events were lower with sac-TMT (3.1% vs 4.9%), and treatment-related deaths occurred in three patients in each arm.^1,2

In a BioPharm International® interview at BIO 2026, Sabeen Mekan, MD, senior vice president and chief medical officer of Zymeworks, pointed to where ADC development is heading. “I think the biggest innovation moving forward is on the payload side,” Mekan said.

In April, BioPharm International reported Phase 1/2 data for another ADC in this indication, BioNTech and DualityBio’s HER2-directed trastuzumab pamirtecan.

What happens next?

FDA has accepted a Biologics License Application for sac-TMT for priority review in adults with endometrial cancer previously treated with platinum-containing chemotherapy and a PD-1 or PD-L1 inhibitor, with a target action date of June 15, 2027.¹ Sac-TMT is being evaluated in 18 ongoing global phase 3 trials, 10 of them in women’s cancers.^1,4

References

1. Sacituzumab tirumotecan (sac-TMT) reduced the risk of death by 32% and the risk of disease progression or death by 41% compared to chemotherapy in certain patients with advanced or recurrent endometrial cancer. News release. Merck & Co., Inc. October 26, 2026. Accessed October 26, 2026.
2. Next-Gen Drug Significantly Prevents Return of and Death From Endometrial Cancer. News release. NYU Langone Health. October 26, 2026. Accessed October 26, 2026.
3. Cancer stat facts: uterine cancer. National Cancer Institute Surveillance, Epidemiology, and End Results Program. Accessed October 26, 2026.
4. Merck, Kelun score with sac-TMT in endometrial cancer trial. Fierce Pharma. Published May 18, 2026. Accessed October 26, 2026.
5. Sacituzumab tirumotecan (MK-2870) in post platinum and post immunotherapy endometrial cancer (MK-2870-005). ClinicalTrials.gov. Accessed October 26, 2026.
6. 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 & Co., Inc. May 18, 2026. Accessed October 26, 2026.