Women with advanced or recurrent endometrial cancer lived longer on sacituzumab tirumotecan than on standard single-drug chemotherapy in a large Phase 3 trial, according to results published in The Lancet and presented at the ESMO 2026 congress. The study group was narrowly defined: every participant’s cancer had already progressed after platinum chemotherapy and after anti-PD-1 or anti-PD-L1 immunotherapy, the two treatments that anchor care for this disease.
Median overall survival reached 19.0 months with sacituzumab tirumotecan, sold in the trial under the short name sac-TMT, compared with 12.1 months on chemotherapy. That difference corresponded to a hazard ratio of 0.68 (95% CI, 0.55 to 0.84), meaning the risk of death at any point during follow-up was about one-third lower in the sac-TMT group. The drug is a TROP2-directed antibody-drug conjugate developed by Merck with Kelun-Biotech.
The trial, called TroFuse-005, randomized 776 women: 386 received sac-TMT on its own and 390 received a physician’s choice of doxorubicin or paclitaxel. It was run as ENGOT-en23/GOG-3095 and registered as NCT06132958. The figures come from a pre-specified interim analysis with a data cutoff of March 23, 2026, and a median follow-up of 14.0 months, so the survival curves are still maturing.
Secondary results pointed the same way. Median progression-free survival was 7.2 months on sac-TMT against 3.9 months on chemotherapy (HR 0.59; 95% CI, 0.50 to 0.70). Tumors shrank measurably in 35.1 percent of sac-TMT patients versus 17.3 percent on chemotherapy, and responses lasted a median of 11.1 months compared with 6.9 months. Eligibility did not hinge on mismatch-repair status, which separates this study from trials built around immunotherapy for dMMR tumors.
The benefit arrived with a real side-effect burden. Severe, grade 3 or higher treatment-related side effects occurred in 54.4 percent of sac-TMT patients versus 41.4 percent on chemotherapy. Anemia was the most common problem, reported in 71.4 percent of the sac-TMT group at any grade, with grade 3 or higher treatment-related anemia in 20.8 percent. Mouth sores affected roughly 55 percent, with grade 3 stomatitis in 9.9 percent. Toxicity on the surface of the eye appeared in 30.5 percent, and lung inflammation was uncommon but present at 1.8 percent. Fewer patients stopped sac-TMT because of side effects than stopped chemotherapy (3.1 versus 4.9 percent), treatment-related deaths were 0.8 percent in both arms, and quality-of-life scores were maintained in both groups.
Trial investigators Lorusso and Pothuri describe the results as practice-changing for a group that has largely exhausted standard options. Specialists who were not running the study urge restraint. Independent ESMO discussant Joyce Liu of Dana-Farber cautioned that the toxicity looks much like real chemotherapy, questioned whether the small carcinosarcoma subgroup benefits, and noted that six similar antibody-drug conjugates are already in Phase 3 testing. Oncologist Kathleen Moore has likewise warned that the mouth, eye and blood toxicities will require aggressive, organized management rather than casual prescribing.
Regulatory review is under way but incomplete. Sac-TMT is not approved in the United States for this use. The FDA has accepted Merck’s application and granted Priority Review, with a decision targeted for June 15, 2027. The drug is already approved in China for other cancers.
For patients, the careful reading is this: in a sponsor-run interim analysis, one targeted drug beat one-drug chemotherapy by roughly seven months of median survival in women whose cancer had progressed past both platinum chemotherapy and immunotherapy. That is a meaningful gain in a later-line setting, and it comes with substantial toxicity that clinics will have to prevent and treat actively. Whether the advantage holds with longer follow-up, and how sac-TMT compares with the wave of similar drugs behind it, remains open.
Sources: The Lancet, TroFuse-005 trial publication; ESMO 2026 Presidential Symposium abstract LBA11; Merck announcement, Oct. 26, 2026
