Merck (NYSE: MRK) reported that sacituzumab tirumotecan endometrial cancer data from the Phase III TroFuse-005 trial met both co-primary endpoints of overall survival and progression-free survival versus chemotherapy, marking the first time a TROP2-directed antibody-drug conjugate has demonstrated a statistically significant survival benefit in this setting. The readout positions sac-TMT as a potential new standard of care for patients with advanced or recurrent endometrial cancer who have exhausted platinum-based chemotherapy and immunotherapy — a population with few established options.
Sac-TMT was developed by Kelun-Biotech (6990.HK), a subsidiary of Kelun Pharmaceutical (002422.SZ), and licensed to Merck for development in all territories outside of Greater China in a 2022 deal. The readout represents the first Phase III data to be reported by Merck for the program.
TroFuse-005 (NCT06132958) is a randomized, active-controlled, open-label, multicenter global Phase III trial evaluating sac-TMT against treatment of physician's choice (TPC) — consisting of doxorubicin or paclitaxel — in 776 patients with endometrial carcinoma and carcinosarcoma who had previously received platinum-based chemotherapy and anti-PD-1/PD-L1 immunotherapy, either together or separately.
At a pre-specified interim analysis, sac-TMT met both co-primary endpoints with statistically significant and, according to Merck, clinically meaningful improvements in OS and PFS by blinded independent central review versus TPC. The trial also reached its key secondary endpoint of objective response rate. Merck did not disclose specific numerical values — hazard ratios, median survival estimates, or response rates — in the press release; full data are expected to be presented at an upcoming medical meeting.
The safety profile was consistent with prior sac-TMT studies, with no new safety signals identified. Detailed adverse event data were not released.
The endometrial cancer treatment context
The TroFuse-005 readout arrives at a moment of rapid evolution in endometrial cancer treatment, but one that has left a specific patient population poorly served. First-line approvals for advanced or recurrent disease have accumulated quickly — Merck's own Keytruda (pembrolizumab) combined with carboplatin and paclitaxel, GSK's Jemperli (dostarlimab) plus chemotherapy, and AstraZeneca's durvalumab-based regimen have each secured regulatory clearance in the front-line setting over the past two years. These approvals, however, do not address patients who progress after both platinum-based chemotherapy and immunotherapy.
In that later-line setting, options are narrow. Eisai and Merck's Lenvima (lenvatinib) combined with pembrolizumab carries approval for pMMR/non-MSI-H endometrial carcinoma after prior systemic therapy, but its pivotal trial excluded carcinosarcoma and enrolled a population that was largely immunotherapy-naïve — limiting its applicability to patients who have already received a checkpoint inhibitor. Karyopharm's Xpovio (selinexor), an XPO1 nuclear export inhibitor, is approved in the post-platinum, post-immunotherapy setting and explicitly includes carcinosarcoma, but carries a meaningful tolerability burden including nausea, fatigue, and thrombocytopenia.
TroFuse-005 enrolled both endometrial carcinoma and carcinosarcoma patients, a design choice that, if reflected in the eventual label, would address a gap that lenvatinib plus pembrolizumab does not cover.