Clinical Summary: 

• Design/Population: The phase 3 TroFuse-005 trial evaluated sacituzumab tirumotecan, a TROP2-directed antibody-drug conjugate, versus physician's choice chemotherapy in patients with advanced or recurrent endometrial cancer previously treated with platinum-based chemotherapy and anti–PD-1/PD-L1 therapy.

• Key Outcomes: Sacituzumab tirumotecan significantly improved progression-free survival, overall survival, and objective response, reducing the risk of disease progression or death by 41% and the risk of death by 32% compared with physician-selected chemotherapy. Grade ≥3 treatment-related adverse events were more frequent with sacituzumab tirumotecan.

• Clinical Relevance: These findings support sacituzumab tirumotecan as a potential new treatment option for patients with advanced or recurrent endometrial cancer following platinum-based chemotherapy and immunotherapy, demonstrating improved survival and antitumor activity compared with conventional chemotherapy.

Results from the phase 3 TroFuse-005 trial demonstrated that sacituzumab tirumotecan significantly improved survival and response compared with physician's choice chemotherapy in patients with previously treated advanced or recurrent endometrial cancer, supporting the TROP2-directed antibody-drug conjugate as a potential new treatment option.

These findings were presented by Domenica Lorusso, MD, PhD, Humanitas University, Rozzano, Italy, during a Presidential Symposium at the European Society for Medical Oncology (ESMO) Congress.

In this trial, 776 patients with advanced or recurrent endometrial carcinoma, including carcinosarcoma, who had previously received platinum-based chemotherapy and anti–PD-1/PD-L1 therapy were randomized 1:1 to receive either 4 mg/kg of sacituzumab tirumotecan every 2 weeks (n = 386) or physician-selected chemotherapy (n = 390).

Eligible patients had received up to 3 prior lines of therapy, with platinum-based chemotherapy and immunotherapy administered either separately or in combination.

Physician-selected treatment consisted of 60 mg/m² of doxorubicin every 3 weeks or 80 mg/m² of paclitaxel on days 1, 8, and 15 of each 4-week cycle. Treatment continued until disease progression or unacceptable toxicity. Randomization was stratified by mismatch repair status, TROP2 expression, prior lines of therapy, and baseline disease status.

Dual primary end points were progression-free survival (PFS), as assessed via blinded independent central review, and overall survival (OS). Key secondary end points included objective response rate (ORR), as assessed via blinded independent central review, and safety. 

At a median follow-up of 14 months, median PFS was 7.2 months in the sacituzumab tirumotecan arm and 3.9 months in the physician's choice chemotherapy arm, reducing the risk of disease progression or death by 41% (hazard ratio [HR], 0.59; 95% confidence interval [CI], 0.50 to 0.70; P < .0001).

A significant OS benefit was also observed with sacituzumab tirumotecan. Median OS was 19 months compared with 12.1 months with physician's choice chemotherapy, corresponding to a 32% reduction in the risk of death (HR, 0.68; 95% CI, 0.55 to 0.84; P = .0001).

Among patients evaluable for response, ORR was 35.1% in the sacituzumab tirumotecan arm and 17.3% in the physician's choice chemotherapy arm, representing an absolute difference of 17.8 percentage points (P < .00001).

Responses were also more durable with sacituzumab tirumotecan. Median duration of response was 11.1 months compared with 6.9 months with physician's choice chemotherapy.

At 6 months, 69% of responders receiving sacituzumab tirumotecan maintained their response compared with 53.2% receiving physician's choice chemotherapy. At 12 months, the corresponding rates were 42.9% and 35.1%, respectively. 

Treatment-related adverse events occurred in 97.1% of patients receiving sacituzumab tirumotecan compared with 89.6% receiving physician's choice chemotherapy. Grade ≥3 treatment-related adverse events were reported in 54.4% and 41.4% of patients, respectively.

Anemia was the most commonly reported grade ≥3 adverse event in both groups, occurring in 20.8% of patients receiving sacituzumab tirumotecan compared with 13.4% receiving physician's choice chemotherapy.

Treatment-related adverse events led to treatment discontinuation in 3.1% of patients receiving sacituzumab tirumotecan and 4.9% receiving physician-selected chemotherapy. Treatment-related deaths occurred in 0.8% of patients in both groups.

Median treatment duration was 31.1 weeks with sacituzumab tirumotecan compared with 15 weeks with physician-selected chemotherapy. Global health status and quality of life were maintained over time in both treatment groups.

Investigators concluded that sacituzumab tirumotecan demonstrated statistically significant and clinically meaningful improvements in PFS, OS, and ORR compared with physician's choice chemotherapy, with a manageable safety profile, supporting the antibody-drug conjugate as a new treatment option for patients with previously treated advanced or recurrent endometrial cancer.

Source: 

Lorusso D, Martin-Babau J, Backes F, 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 ESMO Congress. October 23-27, 2026; Madrid, Spain. LBA11.