At the ESMO Congress 2026 Presidential Symposium III, Domenica Lorusso (Pieve Emanuele, Italy) presented results from the phase III TroFuse-005/ENGOT-en23/GOG-3095 trial (NCT06132958), evaluating sacituzumab tirumotecan (sac-TMT), a TROP2-targeted antibody–drug conjugate (ADC), in patients with previously treated advanced or recurrent endometrial cancer.
The investigational therapy demonstrated statistically significant improvements in both overall survival (OS) and progression-free survival (PFS) compared with chemotherapy, achieving a median OS of 19.0 versus 12.1 months and median PFS of 7.2 versus 3.9 months.
Methods
TroFuse-005 is a randomized phase III trial evaluating the efficacy and safety of sacituzumab tirumotecan in patients with advanced or recurrent endometrial cancer who had previously received platinum-based chemotherapy and anti-PD-1/PD-L1 immunotherapy.
Eligible patients, including those with carcinosarcoma, had received no more than three prior lines of systemic treatment.
A total of 776 patients were randomized 1:1 to receive:
- Sacituzumab tirumotecan: 4 mg/kg intravenously every two weeks.
- Treatment of physician’s choice: Doxorubicin 60 mg/m² every three weeks or paclitaxel 80 mg/m² on days 1, 8, and 15 of each four-week cycle.
Treatment continued until disease progression or unacceptable toxicity.
Randomization was stratified by mismatch repair status, TROP2 expression, prior treatment lines, and baseline disease status.
The dual primary endpoints were PFS assessed by blinded independent central review and overall survival. Objective response rate was the key secondary endpoint.
Key Takeaways
At the March 23, 2026, data cutoff, 776 patients had been randomized to sacituzumab tirumotecan (n=386) or treatment of physician’s choice (n=390). Median follow-up was 14.0 months.
- Overall survival: Median OS was 19.0 months with sacituzumab tirumotecan versus 12.1 months with chemotherapy (HR 0.68; 95% CI, 0.55–0.84; p=0.0001), representing a 6.9-month improvement.
- Progression-free survival: Median PFS was 7.2 versus 3.9 months, respectively (HR 0.59; 95% CI, 0.50–0.70; p<0.0001), corresponding to a 41% reduction in the hazard of disease progression or death.
- PFS rates: Six-month PFS was 51.2% versus 31.9%, while 12-month PFS was 29.4% versus 12.4%, favoring sacituzumab tirumotecan.
- Objective response rate: ORR was 35.1% with sacituzumab tirumotecan compared with 17.3% with chemotherapy (p<0.00001).
- Duration of response: Median DoR was 11.1 months versus 6.9 months. Responses lasting at least 12 months occurred in 42.9% versus 35.1% of responders.
- Grade ≥3 treatment-related adverse events: Reported in 54.4% of patients receiving sacituzumab tirumotecan compared with 41.4% receiving chemotherapy.
- Anemia: Treatment-emergent anemia occurred in 71.4% versus 46.6% of patients, while grade ≥3 treatment-related anemia occurred in 20.8% versus 13.4%.
- Stomatitis: Treatment-related stomatitis occurred in 54.9% versus 14.4% of patients, including grade 3 events in 9.9% versus 1.6%, respectively.
- Ocular surface toxicity: Treatment-emergent ocular surface toxicity was reported in 30.5% versus 6.8% of patients.
- Interstitial lung disease/pneumonitis: Treatment-emergent events occurred in 1.8% versus 0.5% of patients.
- Treatment discontinuation: Treatment-related adverse events led to discontinuation in 3.1% versus 4.9% of patients. Treatment-related deaths occurred in 0.8% of patients in both groups.
- Quality of life: Global health status and quality-of-life scores were maintained over time in both treatment groups.
Conclusion
The phase III TroFuse-005 trial demonstrated statistically significant and clinically meaningful improvements in overall survival, progression-free survival, and objective response rate with sacituzumab tirumotecan compared with chemotherapy in patients with previously treated advanced or recurrent endometrial cancer.
The 6.9-month improvement in median overall survival, together with a 41% relative reduction in the hazard of disease progression or death, highlights the potential of TROP2-targeted ADC therapy following platinum-based chemotherapy and immunotherapy.
Although treatment discontinuation rates remained low and quality of life was maintained, sacituzumab tirumotecan was associated with higher rates of grade ≥3 treatment-related adverse events. Stomatitis, anemia, and ocular surface toxicity were notable adverse events requiring careful monitoring and management.
These findings support sacituzumab tirumotecan as a potential new treatment option for patients with advanced or recurrent endometrial cancer who have progressed following standard systemic therapies.
Source: ESMO Congress 2026, Abstract LBA11; TroFuse-005/ENGOT-en23/GOG-3095 (NCT06132958).
