An investigational antibody-drug conjugate, sacituzumabtirumotecan (sac-TMT), reduced the risk of death by 32% compared with chemotherapy in patients with previously treated advanced or recurrent endometrial cancer, according to phase 3 findings announced in a Merck press release.

The results come as the US Food and Drug Administration (FDA) accepted a biologics license application for Priority Review of sacituzumab tirumotecan, a TROP2-directed antibody-drug conjugate developed by Merck in collaboration with Kelun-Biotech. The application seeks approval for adults with endometrial cancer previously treated with platinum-containing chemotherapy and a PD-1 or PD-L1 inhibitor, administered separately or in combination. The FDA assigned a target action date of June 15, 2027.

The phase 3 TroFuse-005 trial was a randomized, open-label, multicenter study involving 776 patients with advanced or recurrent endometrial cancer. Participants received either sacituzumab tirumotecan or physician's choice of doxorubicin or paclitaxel. The study's dual primary end points were overall survival and progression-free survival, the latter assessed by blinded independent central review.

At a prespecified interim analysis, after a median follow-up of 14 months, median overall survival was 19 months with sacituzumabtirumotecan versus 12.1 months with chemotherapy, representing a 32% reduction in the risk of death. Median progression-free survival was 7.2 months versus 3.9 months, respectively, representing a 41% reduction in the risk of disease progression or death.

The objective response rate, a key secondary end point, was 35.1% with sacituzumab tirumotecan versus 17.3% with chemotherapy. Complete responses occurred in 6.1% and 4.5% of patients, respectively. Median duration of response was 11.1 months versus 6.9 months.

Grade 3 or higher treatment-related adverse events occurred in 54.4% of patients receiving sacituzumab tirumotecan and 41.4% receiving chemotherapy. The most common severe events with sacituzumab tirumotecan were anemia (23.7%), neutropenia (20.1%), and oral mucositis or stomatitis (9.9%). Treatment-related adverse events led to discontinuation in 3.1% versus 4.9% of patients and were associated with 3 deaths (0.8%) in each group. Merck reported no new safety signals.

In TroFuse-005, sacituzumab tirumotecan was administered at 4 mg/kg on day 1 of each 2-week cycle.

The trial findings were presented at the European Society for Medical Oncology Congress on October 26 and published in The Lancet. The FDA's Priority Review does not constitute approval, and sacituzumab tirumotecan remains investigational.

Sources: Merck, The Lancet