Sac-TMT Earns FDA Priority Review in Pretreated Endometrial Cancer

The FDA has accepted a biologics license application (BLA) under priority review for sacituzumab tirumotecan (sac-TMT) as a treatment for adults with endometrial cancer who previously received platinum-containing chemotherapy and a PD-1 or PD-L1 inhibitor, given separately or in combination, according to a news release from Merck.^1,2 The FDA set a target action date of June 15, 2027, under the Prescription Drug User Fee Act, and Merck stated that it is in discussions with the FDA and hopeful for an earlier approval.

The application is supported by the phase 3 TroFuse-005/ENGOT-en23/GOG-3095 trial (NCT06132958). Data from the trial were most recently presented at the Presidential Symposium at the European Society for Medical Oncology (ESMO) 2026 Congress, and simultaneously published in The Lancet.^3,4

What did the TroFuse-005 trial show?

At a median follow-up of 14.0 months, the median overall survival (OS) was 19.0 months (95% CI, 16.1-not reached) with sac-TMT vs 12.1 months (95% CI, 11.0-15.2) with treatment of physician's choice (TPC), corresponding to a 32% reduction in the risk of death (HR, 0.68; 95% CI, 0.55-0.84; P = .0001). The median progression-free survival (PFS) by blinded independent central review was 7.2 months (95% CI, 5.6-7.6) vs 3.9 months (95% CI, 3.7-5.3), respectively, for a 41% reduction in the risk of progression or death (HR, 0.59; 95% CI, 0.50-0.70; P <.0001).

The objective response rate was 35.1% with sac-TMT vs 17.3% with TPC, for a difference of 17.8 percentage points (95% CI, 11.6-23.9; P <.00001), including complete responses in 6.1% vs 4.5%. The median duration of response was 11.1 months (95% CI, 9.2-13.0) vs 6.9 months (95% CI, 5.4-9.1) in the sac-TMT and TPC arms, respectively.

What was the TroFuse-005 trial design?

TroFuse-005 is a randomized, open-label, phase 3 trial that enrolled 776 patients at 242 gynecologic oncology centers across 31 countries and regions. Eligible patients were 18 years or older with histologically confirmed advanced or recurrent endometrial carcinoma or carcinosarcoma who had received up to 3 prior lines of therapy, including systemic platinum-based chemotherapy and anti–PD-1 or anti–PD-L1 therapy.

Patients were randomly assigned 1:1 to intravenous sac-TMT at 4 mg/kg on days 1 and 15 of each 28-day cycle or to TPC, consisting of doxorubicin at 60 mg/m² every 3 weeks or paclitaxel at 80 mg/m² on days 1, 8, and 15 of each 28-day cycle. Randomization was stratified by mismatch repair status, TROP2 expression by immunohistochemistry, number of prior lines of systemic therapy, and baseline disease status. OS and PFS were dual primary end points, and objective response rate was a key secondary end point.

What adverse effects were reported with sac-TMT?

Treatment-related adverse effects (TRAEs) of any grade occurred in 97.1% of patients receiving sac-TMT vs 89.6% of those receiving TPC, with grade 3 or higher TRAEs in 54.4% vs 41.4%. The most common grade 3 or higher TRAEs with sac-TMT were anemia (23.7%), neutropenia (20.1%), and oral mucositis or stomatitis (9.9%).

Discontinuation due to TRAEs occurred in 3.1% of the sac-TMT arm vs 4.9% of the TPC arm, and TRAEs led to death in 0.8% of patients in each arm. Health-related quality of life was maintained over time with sac-TMT. No new safety signals were identified.

What is sac-TMT and how does it work?

Sac-TMT is an investigational antibody-drug conjugate directed at TROP2, a protein overexpressed on many tumor cells relative to healthy cells. Its payload is a belotecan-derived topoisomerase I inhibitor, and a bifunctional linker is designed to maximize delivery of that payload to tumor cells while limiting release during circulation. Sac-TMT was developed by Kelun-Biotech, which granted Merck exclusive rights outside Greater China.

References

1. Merck & Co, Inc, Rahway, NJ, USA announces third-quarter 2026 financial results; highlights multiple milestones advancing broad, diverse pipeline. News release. Merck & Co, Inc. October 29, 2026. Accessed November 3, 2026. https://tinyurl.com/mtv8hbx5
2. 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. News release. Merck & Co, Inc. October 26, 2026. Accessed November 3, 2026. https://tinyurl.com/2ffhwtky
3. 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: 2026 European Society for Medical Oncology Congress; October 23-27, 2026; Madrid, Spain. Abstract LBA11.
4. Lorusso D, Martin-Babau J, Backes F, et al. Sacituzumab tirumotecan versus treatment of physician's choice in previously treated endometrial cancer (TroFuse-005/ENGOT-en23/GOG-3095): a randomised, open-label, phase 3 trial. Lancet. Published online October 26, 2026. doi:10.1016/S0140-6736(26)02099-4