Sacituzumab Tirumotecan Improves Survival in Advanced Endometrial Cancer

The TROP2-directed antibody-drug conjugate (ADC) sacituzumab tirumotecan (sac-TMT) demonstrated a statistically significant and clinically meaningful improvement in both overall survival (OS) and progression-free survival (OS) vs chemotherapy in patients with advanced or recurrent endometrial cancer who had previously received platinum-based chemotherapy and anti–PD-1/PD-L1 immunotherapy, according to results from the global phase 3 TroFuse-005 trial (NCT06132958).¹

The trial also met its key secondary end point of objective response rate (ORR). The safety profile observed was consistent with data from prior sac-TMT studies, with no new safety signals identified. Specific and have not yet been released and will be presented at an upcoming medical meeting.

"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. 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," 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, stated in a news release.

TroFuse-005 Trial Design

TroFuse-005 is a randomized, active-controlled, open-label, multicenter, global phase 3 trial that enrolled 776 patients with endometrial carcinoma and carcinosarcoma who had previously received platinum-based chemotherapy and anti-PD-1/PD-L1 immunotherapy either concurrently or sequentially.1 Patients were randomized to receive either sac-TMT or treatment of physician's choice (TPC), consisting of doxorubicin or paclitaxel. Sac-TMT was administered at 4 mg/kg on Day 1 of each two-week cycle. Doxorubicin was dosed at 60 mg/m² on Day 1 of each three-week cycle, while paclitaxel was administered at 80 mg/m² on Days 1, 8, and 15 of each four-week cycle.

The trial has dual primary endpoints of PFS and OS. The key secondary end point was ORR; additional secondary endpoints included duration of response, adverse event incidence, treatment discontinuation due to adverse events, and change from baseline in global health status and quality-of-life scores.

Mechanism of Sac-TMT and Rationale for Launching TroFuse-005

Sac-TMT targets TROP2, a protein highly overexpressed across many solid tumors. The ADC delivers a belotecan-derived topoisomerase I inhibitor payload via a proprietary bifunctional linker designed to maximize tumor cell payload delivery while minimizing systemic release.¹

The clinical rationale for TroFuse-005 was established through the phase 1/2 KL264-01 trial (NCT04152499), which evaluated sac-TMT across a range of solid tumors including endometrial cancer. At the 2024 ESMO Annual Congress, investigators reported that among 44 patients with previously treated advanced endometrial cancer enrolled in the trial at a median follow-up of 7.2 months, sac-TMT monotherapy achieved an investigator-assessed ORR of 34.1%, a confirmed ORR of 27.3%, and a disease control rate of 75.0%.² The partial response rate was 34.1% and the stable disease rate was 40.9%.

The median PFS was 5.7 months (95% CI, 3.7-9.4), with a 6-month PFS rate of 47.5%. More than half of enrolled endometrial patients (52.3%) had received two or more prior lines of therapy, underscoring the heavily pretreated nature of the study population. TROP2 expression by IHC H-score greater than 200 was associated with numerically higher ORRs (41.7% vs 35.7% for H-score ≤200), though responses were observed regardless of TROP2 expression level.

Additional phase 2 data from a larger expanded endometrial cancer cohort of 158 patients presented at the 2025 CCHIO Congress showed confirmed ORRs of 30.7% and 34.1% in patients receiving sac-TMT at 4 mg/kg and 5 mg/kg, respectively, with median DOR of 9.3 months and 8.7 months and median PFS of 6.0 months and 7.3 months in the respective dose groups.³

Across both dose levels, all responses were partial responses, and the safety profile was described as manageable, with the most common treatment-related adverse events across studies including anemia, decreased white blood cell count, nausea, and alopecia, without grade 5 treatment-related events.^2,3

"These findings [from TroFuse-005] 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,” Dean Y. Li, MD, PhD, president of Merck Research Laboratories, the developer of sac-TMT, stated in a press release.

REFERENCES

1. Merck. 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/yxhm32at

2. Wang D, Wang K, An R, et al. Safety and efficacy of sacituzumab tirumotecan (sac-TMT) in patients with previously treated advanced endometrial carcinoma and ovarian cancer from a phase II study. Ann Oncol. 2024;35(suppl 2):S548. doi:10.1016/j.annonc.2024.08.777

3/ Kelun-Biotech. Kelun-Biotech presented TROP2 ADC sacituzumab tirumotecan results from multiple clinical studies at the 2025 CCHIO Congress. News release. Kelun-Biotech; November 10, 2025. Accessed May 18, 2026. https://tinyurl.com/mzfm6w24