ESMO 2026: Sacituzumab Tirumotecan Extends Survival By 6.9 Months Versus Chemotherapy In Endometrial Cancer

A New Option for Endometrial Cancer Progressing After Platinum and Immunotherapy: The Antibody-Drug Conjugate Sac-TMT Outperformed Chemotherapy

Sacituzumab tirumotecan (sac-TMT), a TROP2-directed antibody-drug conjugate from Merck and Kelun-Biotech, significantly improved both overall survival and progression-free survival compared with physician's choice chemotherapy in advanced or recurrent endometrial cancer that progressed after platinum chemotherapy and anti-PD-(L)1 immunotherapy. The full results of the phase 3 TroFuse-005 trial were presented on October 26, 2026 at the ESMO Congress (LBA11) and published in The Lancet. Median overall survival was 19.0 versus 12.1 months (HR 0.68) and median progression-free survival 7.2 versus 3.9 months (HR 0.59); the price was more frequent grade 3 or higher adverse events. The drug is not yet approved for this indication. We have previously covered immunotherapy and antibody-drug conjugate treatments.

Why does this matter?

Endometrial (uterine lining) cancer is one of the gynecologic cancers becoming more common worldwide. In the US, about 68,270 new cases of uterine cancer and 14,450 losses of life are expected in 2026, and the rate of loss of life has risen by about 1.3% per year over the past decade. For disease that has spread to distant organs, 5-year relative survival is 19.9% (SEER data).

In the first line, platinum-based chemotherapy combined with immunotherapy is used. When the disease progresses after these treatments, options are limited; commonly used choices are chemotherapies such as doxorubicin or paclitaxel, as in the control arm of TroFuse-005. Some mismatch repair–deficient (dMMR) endometrial cancers are linked to hereditary Lynch syndrome (hereditary cancers); immunotherapy works strongly in these tumors (we have previously covered dostarlimab approval in dMMR rectal cancer). The trial asked whether a new drug could beat chemotherapy after these treatments.

Sac-TMT is an antibody-drug conjugate (ADC) that links an antibody recognizing TROP2, a protein highly expressed in many solid tumors, to a belotecan-derived topoisomerase I inhibitor payload through a specialized linker. It was developed by Kelun-Biotech; Merck holds exclusive rights outside Greater China. It has received four approvals in China since November 2024, in breast and non-small cell lung cancer.

What is sacituzumab tirumotecan and how does it work in endometrial cancer?

Sacituzumab tirumotecan (sac-TMT) is an antibody-drug conjugate that links a TROP2-recognizing antibody to a topoisomerase I inhibitor payload. In TroFuse-005 it was given intravenously (4 mg/kg) every 2 weeks to patients whose endometrial cancer progressed after platinum chemotherapy and immunotherapy, and it raised median overall survival from 12.1 to 19.0 months compared with chemotherapy. It is not yet approved.

What are the results based on? The TroFuse-005 trial

Results

At the prespecified interim analysis (data cutoff March 23, 2026), median overall survival was 19.0 months (95% CI 16.1–not reached) with sac-TMT and 12.1 months (95% CI 11.0–15.2) with chemotherapy (HR 0.68; 95% CI 0.55–0.84; p<0.0001). That is a 32% relative reduction in the risk of loss of life and an absolute gain of 6.9 months in median survival. Median progression-free survival was 7.2 versus 3.9 months (HR 0.59; 95% CI 0.50–0.70): the risk of progression or loss of life fell by 41% in relative terms, and the median time gained was 3.3 months.

Progression-free survival at 6 months was 51.2% versus 31.9%, and at 12 months 29.4% versus 12.4%; the share of patients alive without progression at 12 months rose about 2.4-fold (roughly 17 more patients per 100). The objective response rate was 35.1% versus 17.3%, and among responders the median duration of response was 11.1 versus 6.9 months. Global health status and quality-of-life scores were maintained over time in both arms (according to reports of the ESMO presentation).

Safety

Grade 3 or higher treatment-related adverse events occurred in 54.4% of the sac-TMT arm and 41.4% of the chemotherapy arm (a 13.0-point difference). Anemia (23.7%), neutropenia (20.1%) and stomatitis (9.9%) were the most frequent grade 3 or higher events. Across all grades, stomatitis was 54.9% versus 14.4%, ocular surface toxicity 30.5% versus 6.8% and anemia 71.4% versus 46.6%; interstitial lung disease or pneumonitis was uncommon (1.8% and 0.5%).

Discontinuation because of adverse events was lower in the sac-TMT arm (3.1% vs 4.9%). Early recognition and management of mouth and eye side effects matter particularly with this drug class; detailed recommendations will become clear in the prescribing information after a possible approval.

How should the results be read?

Strengths

• A large (776 patients), global, randomized phase 3 trial with consistent benefit across both primary endpoints.
• An overall survival benefit was shown, which is rare in this patient population; the median difference is 6.9 months.
• The control arm consisted of standard chemotherapies still used today (doxorubicin or paclitaxel); all patients had previously received platinum and anti-PD-(L)1 therapy.
• Response rate, duration of response and progression-free survival rates all pointed in the same direction; quality-of-life scores were maintained.

Points of caution

• Interim analysis and short follow-up: Median follow-up is 14.0 months; the tail of the survival curves and the durability of benefit are uncertain.
• Open-label design: Patients and physicians knew the treatment, although measuring progression-free survival by blinded independent central review reduces the risk of bias.
• More adverse events: Grade 3 or higher treatment-related adverse events were about 13 points more frequent; mouth sores and ocular surface problems were common.
• Subgroups: Results by mismatch repair status, TROP2 expression, histology (including carcinosarcoma) and number of prior lines are not detailed in the sources we could access.
• Comparator: The control arm was chemotherapy; there was no direct comparison with other second-line options.

What does this mean in practice?

• Not yet approved: The FDA reportedly accepted the application for priority review with a target action date of June 15, 2027 (according to Merck). Until approval, access is limited to clinical trials.
• Patient profile: The results apply to patients who progressed after platinum and anti-PD-(L)1 therapy and had at most 3 prior lines; they cannot be directly applied to patients outside this profile.
• Treatment plan: An intravenous infusion every 2 weeks; blood count monitoring and mouth and eye care will be part of managing side effects.
• Prior immunotherapy: In patients who previously received immunotherapy, a record of past immune-related side effects is important (side effects of immunotherapy).
• Future trials: TroFuse-033 compares sac-TMT + pembrolizumab with pembrolizumab alone in first-line mismatch repair–proficient (pMMR) endometrial cancer; its primary completion is estimated for 2032.

Practical recommendations for patients and their families

• If your endometrial cancer has progressed after platinum chemotherapy and immunotherapy, find out your tumor's mismatch repair status (dMMR/pMMR) and your prior lines of treatment; eligibility for new trials depends on this information.
• Ask your physician about options after progression, clinical trial opportunities and the side effect profile of antibody-drug conjugates.
• Contact your team right away for symptoms such as mouth sores or pain, dry or burning eyes, blurred vision, fever or marked fatigue.
• The results cover a specific group of patients; news about a new drug does not mean it is right for you. Assess suitability together with your oncologist.
• Do not hesitate to get a second opinion when making decisions.
• When choosing treatment, look not only at survival time but also at side effects, your quality of life and the impact on your daily life.

Frequently asked questions

What did the TroFuse-005 trial show?

In advanced or recurrent endometrial cancer that progressed after platinum and immunotherapy, sac-TMT extended median overall survival to 19.0 versus 12.1 months (HR 0.68) and median progression-free survival to 7.2 versus 3.9 months (HR 0.59) compared with physician's choice chemotherapy. The objective response rate was 35.1% versus 17.3%.

What are the side effects of sac-TMT?

Grade 3 or higher treatment-related adverse events occurred in 54.4% versus 41.4%. Anemia, neutropenia, mouth sores and ocular surface problems stood out; discontinuation because of adverse events was low (3.1% vs 4.9%).

Are sacituzumab tirumotecan and sacituzumab govitecan (Trodelvy) the same drug?

No. Both are antibody-drug conjugates that recognize TROP2, but they are different drugs carrying different payloads and cannot be substituted for each other. The TroFuse-005 results apply only to sacituzumab tirumotecan.

Can this treatment be used in Türkiye?

To our knowledge, no: sacituzumab tirumotecan has no license or reimbursement in Türkiye. The FDA target action date is June 15, 2027; access in Türkiye will become clearer after that. For now, clinical trials may be an option.

Glossary

Antibody-drug conjugate (ADC)

A treatment in which an antibody that recognizes a protein on the tumor cell surface is linked to a potent drug payload through a specialized linker; the drug is delivered to the target cell.

TROP2

A cell surface protein found at high levels in many solid tumors; the target recognized by sac-TMT.

Topoisomerase I inhibitor

A type of drug that blocks an enzyme needed for DNA copying and so stops dividing cells from multiplying; the payload of sac-TMT belongs to this group.

Overall survival

The time from the start of treatment (here, randomization) to loss of life from any cause.

Progression-free survival

The time after starting treatment during which the disease does not progress and no loss of life occurs.

Objective response rate

The proportion of patients whose tumors shrink by a measurable amount.

HR (hazard ratio)

The ratio of the rate at which an event (progression or loss of life) occurs in the two treatment arms; a value below 1 favors the new treatment.

dMMR / pMMR

Deficient (dMMR) or proficient (pMMR) mismatch repair, the system that corrects DNA copying errors.