Sac-TMT reduced risk of progression or death by 41% in TroFuse-005
Overview
In the phase 3 TroFuse-005 trial, investigational sacituzumab tirumotecan (sac-TMT) improved median progression-free and overall survival compared with physician’s-choice chemotherapy in previously treated advanced or recurrent endometrial cancer. The FDA accepted a biologics license application for Priority Review; the drug remains investigational and is not FDA-approved for this indication.
Background
Advanced or recurrent endometrial cancer has been studied in trials of chemotherapy, immunotherapy, and targeted combinations. Related phase 3 studies have evaluated checkpoint inhibitors with chemotherapy in the first-line setting, including durvalumab in DUO-E and dostarlimab-based treatment. In the United States, the FDA approved pembrolizumab with carboplatin and paclitaxel, followed by pembrolizumab maintenance, for primary advanced or recurrent endometrial carcinoma in June 2024. Sac-TMT is being evaluated after prior platinum-containing chemotherapy and PD-1 or PD-L1 inhibitor treatment.
Data Highlights
| Outcome | Sac-TMT | Chemotherapy |
|---|---|---|
| Patients enrolled | 776 total in trial | 776 total in trial |
| Median overall survival | 19 months | 12.1 months |
| Risk reduction in death | 32% | — |
| Median progression-free survival | 7.2 months | 3.9 months |
| Risk reduction in progression or death | 41% | — |
| Objective response rate | 35.1% | 17.3% |
| Complete response rate | 6.1% | 4.5% |
| Median duration of response | 11.1 months | 6.9 months |
| Grade 3 or higher treatment-related adverse events | 54.4% | 41.4% |
| Treatment-related adverse events leading to discontinuation | 3.1% | 4.9% |
| Treatment-related deaths | 3 (0.8%) | 3 (0.8%) |
Key Findings
- TroFuse-005 was a randomized, open-label, multicenter phase 3 trial of 776 patients with advanced or recurrent endometrial cancer; participants received sac-TMT or physician’s choice of doxorubicin or paclitaxel.
- At a prespecified interim analysis after a median follow-up of 14 months, median overall survival was 19 months with sac-TMT and 12.1 months with chemotherapy, corresponding to a 32% reduction in risk of death.
- Median progression-free survival, assessed by blinded independent central review, was 7.2 months with sac-TMT versus 3.9 months with chemotherapy, corresponding to a 41% reduction in risk of progression or death.
- Objective response rates were 35.1% and 17.3%, respectively; median duration of response was 11.1 months with sac-TMT and 6.9 months with chemotherapy.
- Grade 3 or higher treatment-related adverse events occurred in 54.4% of sac-TMT recipients and 41.4% of chemotherapy recipients. The most common severe events with sac-TMT were anemia (23.7%), neutropenia (20.1%), and oral mucositis or stomatitis (9.9%).
- The FDA accepted the sac-TMT biologics license application for Priority Review, with a target action date of June 15, 2027; Priority Review is not approval, and sac-TMT remains investigational.
Clinical Implications
The reported results concern patients with advanced or recurrent endometrial cancer previously treated with platinum-containing chemotherapy and a PD-1 or PD-L1 inhibitor, the population specified in the application. Sac-TMT is not currently approved for this indication; the trial also reported a higher rate of grade 3 or higher treatment-related adverse events than chemotherapy.
Conclusion
In TroFuse-005, sac-TMT was associated with longer median overall and progression-free survival than physician’s-choice chemotherapy, alongside more grade 3 or higher treatment-related adverse events. Regulatory review is ongoing.
Related Resources & Content
- Merck, Merck Newsroom, 2026 -- 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
- The ASCO Post, 2023 -- PARP inhibitor Plus Immunotherapy Added to Chemotherapy Lowers Risk of Disease Progression in Patients With Advanced Endometrial Cancer
- The ASCO Post, 2024 -- Survival Benefit Emerges With Use of Dostarlimab-gxly Plus Chemotherapy in Advanced or Recurrent Endometrial Cancer
- FDA, 2024 -- FDA Approves Pembrolizumab With Chemotherapy for Primary Advanced or Recurrent Endometrial Carcinoma
- the asco post — Addition of Immunotherapy to Chemotherapy Regimen May Increase Progression-Free Survival in Patients With Advanced or Recurrent Endometrial Cancer
- the asco post — Checkpoint Inhibitors Poised to Change Standard of Care in Advanced Endometrial Cancer
- 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
- FDA Approves Pembrolizumab With Chemotherapy for Primary Advanced or Recurrent Endometrial Carcinoma
- PARP inhibitor Plus Immunotherapy Added to Chemotherapy Lowers Risk of Disease Progression in Patients With Advanced Endometrial Cancer
- Survival Benefit Emerges With Use of Dostarlimab-gxly Plus Chemotherapy in Advanced or Recurrent Endometrial Cancer
- FDA approves pembrolizumab with chemotherapy for primary advanced or recurrent endometrial carcinoma | FDA
- Lenvatinib Plus Pembrolizumab in Previously Treated Advanced Endometrial Cancer: Updated Efficacy and Safety From the Randomized Phase III Study 309/KEYNOTE-775 | Journal of Clinical Oncology
- Combination of immunotherapy and chemotherapy as first-line treatment for advanced or recurrent endometrial cancer: a meta-analysis of phase 3 trials - PMC
- 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.com
- Antibody–drug conjugates for advanced/recurrent high-grade endometrial cancer: potential targets, strategies and challenges | Uterine Research | Springer Nature Link
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