Merck’s sac-TMT reduced the hazard of death by 32% in Phase 3 TroFuse-005, improving survival versus chemotherapy in advanced or recurrent endometrial cancer.
Written By: Kirti Kumbhar, M. Pharm (QA)
Reviewed By: Pharmacally Editorial Team
Merck has reported positive results from the Phase 3 TroFuse-005 trial evaluating sacituzumab tirumotecan (sac-TMT) in adults with advanced or recurrent endometrial cancer previously treated with platinum-based chemotherapy and anti-PD-1 or anti-PD-L1 immunotherapy, administered together or separately.
Sac-TMT is an investigational TROP2-directed antibody-drug conjugate (ADC) developed in collaboration with Kelun-Biotech. The randomized, open-label global trial enrolled 776 patients and compared sac-TMT with treatment of physician’s choice (TPC), comprising doxorubicin or paclitaxel.
TroFuse-005 Demonstrates Improvements in Both Primary Endpoints
At a prespecified interim analysis, with a median follow-up of 14.0 months, sac-TMT improved both primary endpoints, overall survival (OS) and progression-free survival (PFS).
Median OS was 19.0 months with sac-TMT versus 12.1 months with chemotherapy, an absolute difference of 6.9 months. The hazard ratio (HR) for death was 0.68 (95% CI, 0.55–0.84; P<0.0001), corresponding to a 32% reduction in the hazard of death.
Median PFS was 7.2 months versus 3.9 months, respectively (HR, 0.59; 95% CI, 0.50–0.70; P<0.0001), representing a 41% reduction in the hazard of disease progression or death.
According to Merck, TroFuse-005 is the first global Phase 3 trial of a TROP2-directed ADC to demonstrate statistically significant improvements in both OS and PFS over chemotherapy in this treatment setting.
Response Rates and Duration of Benefit
The objective response rate (ORR), a key secondary endpoint, was 35.1% with sac-TMT versus 17.3% with chemotherapy, an absolute difference of 17.8 percentage points (95% CI, 11.6–23.9; P<0.00001). Complete responses occurred in 6.1% and 4.5% of patients, respectively.
Median duration of response was also longer with sac-TMT, at 11.1 months (95% CI, 9.2–13.0) compared with 6.9 months (95% CI, 5.4–9.1) with chemotherapy. These findings suggest that the higher response rate was accompanied by longer response duration, although the interim analysis and follow-up period limit conclusions about long-term benefit.
Safety Profile and Treatment Considerations
Treatment-related adverse events (TRAEs) of any grade occurred in 97.1% of patients receiving sac-TMT and 89.6% receiving chemotherapy. Grade 3 or higher TRAEs occurred in 54.4% and 41.4%, respectively.
The most common grade 3 or higher clinical safety events with sac-TMT were anemia (23.7%), neutropenia (20.1%) and oral mucositis or stomatitis (9.9%).
Treatment discontinuation was reported in 3.1% of patients receiving sac-TMT versus 4.9% receiving chemotherapy. TRAEs led to death in three patients (0.8%) in each treatment arm. Merck reported that adverse events were generally manageable with supportive care and dose modifications, and health-related quality of life was maintained over time.
The lower discontinuation rate does not negate the higher incidence of severe TRAEs. The safety findings indicate that any survival benefit must be weighed against hematologic toxicity and oral mucosal complications.
Trial Design and Regulatory Status
TroFuse-005 (NCT06132958) is a randomized, active-controlled, open-label, multicenter global Phase 3 trial. Sac-TMT was administered at 4 mg/kg on Day 1 of each two-week cycle. Comparator regimens were doxorubicin 60 mg/m² on Day 1 of each three-week cycle or paclitaxel 80 mg/m² on Days 1, 8 and 15 of each four-week cycle. PFS was assessed by blinded independent central review, while OS was defined as time from randomization to death from any cause.
The US Food and Drug Administration (FDA) has accepted Merck’s biologics license application for priority review in adults with endometrial cancer previously treated with platinum-containing chemotherapy and a PD-1 or PD-L1 inhibitor, separately or in combination. The target action date is June 15, 2027. Sac-TMT remains investigational in this indication.
Clinical Interpretation
TroFuse-005 provides clinically relevant evidence that sac-TMT can improve survival outcomes compared with chemotherapy in previously treated advanced or recurrent endometrial cancer. The 6.9-month difference in median OS, together with improvements in PFS and response duration, strengthens the case for regulatory consideration in this population.
However, the findings should be interpreted in the context of a prespecified interim analysis and a median follow-up of 14 months. The higher rate of grade 3 or higher TRAEs also represents an important treatment consideration, despite the low discontinuation rate. Further follow-up will help establish the durability of benefit and clarify the treatment’s place in clinical practice. The results should not be generalized automatically to first-line disease or other endometrial cancer settings.
References
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. Merck., October 26, 2026
Sacituzumab Tirumotecan (MK-2870) in Post Platinum and Post Immunotherapy Endometrial Cancer (MK-2870-005) (TroFuse-005), ClinicalTrials.gov ID NCT06132958
About the Writer
Kirti Kumbhar (LinkedIn) is an M.Pharm graduate with experience in Quality Assurance at Lupin Limited and a strong interest in clinical research, regulatory affairs, and Trial Master File (TMF) management. She has developed knowledge of regulatory documentation, quality systems, compliance, and healthcare research through her professional experience. Passionate about clinical development and continuous learning, Kirti is committed to supporting high-quality healthcare documentation, regulatory excellence, and research-driven healthcare advancements.