Results from the phase 3 TroFuse-005/ENGOT-en23/GOG-3095 trial, presented at the European Society of Medical Oncology Congress 2026 in Madrid, show that sacituzumab tirumotecan (sac-TMT), a TROP2-directed antibody-drug conjugate, significantly improved outcomes compared with treatment of physician’s choice (TPC) in patients with previously treated advanced or recurrent endometrial cancer, including those who had received prior immunotherapy.
Across both dual primary endpoints, sac-TMT demonstrated statistically significant and clinically meaningful gains: median progression-free survival (PFS) improved by 3.3 months and median overall survival (OS) improved by 6.9 months versus TPC. The trial was not placebo-controlled; the comparator arm comprised standard chemotherapy options, doxorubicin or paclitaxel, selected at the treating physician’s discretion.
Key finding
In 776 patients with previously treated advanced or recurrent endometrial cancer, sacituzumab tirumotecan was associated with a 41% lower hazard of disease progression or death (HR, 0.59) and a 32% lower hazard of death (HR, 0.68) compared with standard chemotherapy. Longer follow-up is needed to better characterize the durability of the overall survival benefit, as the upper confidence limit for median OS had not been reached at the data cutoff.
Study Design
| Trial | TroFuse-005/ENGOT-en23/GOG-3095 (NCT06132958); phase 3, randomized, open-label |
|---|---|
| Population | Adults with advanced or recurrent endometrial carcinoma, including carcinosarcoma, with measurable or non-measurable disease and prior platinum-based therapy plus anti–PD-1/PD-L1 therapy (separately or in combination); up to 3 prior lines of therapy permitted; stratified by MMR status, TROP2 expression, prior lines of therapy, and baseline disease status |
| Treatment | Sacituzumab tirumotecan 4 mg/kg Q2W vs. treatment of physician’s choice (doxorubicin 60 mg/m² Q3W or paclitaxel 80 mg/m² on days 1, 8, and 15 Q4W); 1:1 randomization; treatment continued until progression or unacceptable toxicity |
| Primary endpoints | Progression-free survival (PFS) by blinded independent central review (BICR) and overall survival (OS) |
| Key secondary endpoints | Objective response rate (ORR) by BICR |
TroFuse-005 enrolled 776 patients across the two arms (sac-TMT, n=386; TPC, n=390), with a data cutoff of March 23, 2026, and a median follow-up of 14.0 months. The trial was sponsored with support from Merck Sharp & Dohme LLC and was conducted in collaboration with ENGOT and GOG. Sacituzumab tirumotecan employs a bifunctional linker designed to stabilize the drug-to-antibody ratio at approximately 7.4 in circulation and maximize payload delivery to tumor cells.
Results and Safety
Sac-TMT achieved a median PFS of 7.2 months (95% CI, 5.6–7.6) compared with 3.9 months (95% CI, 3.7–5.3) for TPC (HR, 0.59 [95% CI, 0.50–0.70]; P<0.0001). Median OS was 19.0 months (95% CI, 16.1–not reached) with sac-TMT versus 12.1 months (95% CI, 11.0–15.2) with TPC (HR, 0.68 [95% CI, 0.55–0.84]; P=0.0001). ORR was 35.1% with sac-TMT versus 17.3% with TPC, a difference of 17.8 percentage points (95% CI, 11.6–23.9; P<0.00001). Median duration of response was 11.1 months with sac-TMT versus 6.9 months with TPC; 42.9% versus 35.1% of responders maintained response for at least 12 months. Global health status and quality of life were reported to be maintained over time in both arms, though patient-level QoL data were not detailed in the abstract.
The safety profile reflected the active treatment setting. Any treatment-related adverse event (TRAE) was reported in 97.1% of sac-TMT patients and 89.6% of TPC patients. Grade ≥3 TRAEs occurred in 54.4% of patients in the sac-TMT arm versus 41.4% in the TPC arm. Anemia was the most common grade ≥3 TRAE in both groups (20.8% vs. 13.4%). Discontinuation due to TRAEs was low and slightly more frequent in the TPC arm (4.9% vs. 3.1%). Treatment-related deaths occurred in 0.8% of patients in each arm. Median treatment duration was notably longer with sac-TMT (31.1 weeks) than with TPC (15.0 weeks), which may partly reflect the differences in the grade ≥3 TRAE rates between arms. Subgroup-level safety data and detailed adverse event breakdowns beyond anemia were not reported in the abstract.
Clinical Context
Advanced or recurrent endometrial cancer that has progressed after platinum-based chemotherapy and checkpoint inhibitor therapy represents a population with limited effective options. TROP2 is overexpressed in endometrial cancer, providing a rationale for antibody-drug conjugate strategies targeting this antigen. The TroFuse-005 results position sacituzumab tirumotecan as a potential new standard in this later-line setting, with improvements demonstrated across PFS, OS, and ORR versus available chemotherapy.
Several questions remain open. The trial stratified patients by MMR status and TROP2 expression level, but the abstract did not report subgroup outcomes by these biomarkers, leaving uncertainty about which patient subsets derive the greatest benefit. Regulatory submissions and subsequent data presentations will likely address these questions, along with longer-term durability of response and OS follow-up, given that the upper confidence interval for median OS in the sac-TMT arm had not been reached at the time of analysis.
Sources
- Lorusso D, et al. Sacituzumab tirumotecan in previously treated advanced or recurrent endometrial cancer: Results from the phase 3 TroFuse-005/ENGOT-en23/GOG-3095 study. Presented at the European Society of Medical Oncology Congress 2026, Madrid, Spain. Abstract LBA11. View source.