Sacituzumab tirumotecan extended both progression-free and overall survival compared with standard chemotherapy in patients with advanced or recurrent endometrial cancer, according to findings from the phase III TroFuse-005/ENGOT-en23/GOG-3095 trial presented at the ESMO Congress 2026 (Abstract LBA11). A report of the findings was also simultaneously published in The Lancet.
“Our study offers much needed hope to women worldwide living with endometrial cancer, which is increasing in both incidence and mortality,” said study co-investigator Michelle Lightfoot, MD, MPH, Assistant Professor at NYU Grossman School of Medicine and a gynecologic oncologist at Perlmutter Cancer Center.
Background and Study Methods
Sacituzumab tirumotecan is a TROP2-directed antibody-drug conjugate with a bifunctional linker to stabilize the drug-to-antibody ratio and maximize the payload delivery to tumor cells. TROP2 is considered a promising target because it is overexpressed in endometrial cancer.
“The rising death rates from endometrial cancer can be traced to highly aggressive subtypes, which are more commonly seen in Black patients, who also have twice the risk of dying from the disease,” Dr. Lightfoot said. “Antibody-drug conjugates such as sacituzumab tirumotecan are effective in targeting and treating these aggressive cancers to delay its progression and prolong survival when it recurs.”
The international phase III TroFuse-005/ENGOT-en23/GOG-3095 trial enrolled patients with endometrial carcinoma, including carcinosarcoma, who had received platinum and anti–PD-1/PD-L1 therapy and up to three prior lines of therapy total (n = 776). Patients were randomly assigned 1:1 to receive sacituzumab tirumotecan 4 mg/kg every 2 weeks or treatment of physician's choice, including doxorubicin or paclitaxel until disease progression or unacceptable toxicity.
Dual primary endpoints included progression-free survival by blinded independent central review and overall survival. Objective response rate by blinded independent central review was a key secondary endpoint.
Key Findings
Patients were followed for a median of 14 months at data cutoff.
The median progression-free survival with sacituzumab tirumotecan was 7.2 months compared with 3.9 months with physician's choice of treatment (hazard ratio [HR] = 0.59; 95% confidence interval [CI] = 0.50–0.70; P < .0001). The median overall survival was 19.0 months with sacituzumab tirumotecan and 12.1 months with physician's choice of treatment (HR = 0.68; 95% CI = 0.55–0.84; P = .0001).
The objective response rate was 35.1% in the investigational arm and 17.3% in the control arm (P < .0001). The median duration of response was 11.1 months vs 6.9 months with sacituzumab tirumotecan and physician's choice of treatment, respectively
“These positive results from the first phase III trial using sacituzumab tirumotecan after immunotherapy establishes this drug as a new standard treatment in recurrent endometrial cancer,” said study principal investigator Bhavana Pothuri, MD, MS, a gynecologic oncologist at NYU Langone Health.
Treatment-related adverse events were reported in 97.1% of patients in the sacituzumab tirumotecan arm and in 89.6% of patients in the physician's choice of treatment arm; grade 3 or higher events were observed in 54.4% and 41.4% of patients, respectively, with anemia being the most common grade 3 or higher treatment-related adverse event (20.8% vs 13.4%). Treatment-related adverse events led to death in 0.8% of patients in each arm.
In the investigational arm specifically, the most common adverse events were anemia, neutropenia, oral mucositis, stomatitis, and dry or itchy eyes.
Global health status and quality of life was maintained over time in both treatment arms.
“As a result of this practice-changing study, clinical guidelines for endometrial cancer will need to be reassessed to incorporate sacituzumab tirumotecan,” said Dr. Pothuri, Professor in the Department of Obstetrics and Gynecology at NYU Grossman School of Medicine and Medical Director of the Clinical Trials Office at Perlmutter Cancer Center.
DISCLOSURES: Funding support for this study was provided by Merck & Co., the manufacturer of sacituzumab tirumotecan and pembrolizumab. Dr. Pothuri receives salary, research support, and/or consulting fees from AbbVie, Acrivon, Agenus, Alkermes, AstraZeneca, BeiGene, BioNTech, Celgene, Celsion/Imunon, Corcept, Cybrexa, Daiichi Sankyo, Duality Bio, Eisai, Genmab, GOG Partners, GSK, ImmunoGen/AbbVie, Imvax, Incyclix Bio, Incyte, InxMed, Karyopharm, Loxo@Lilly, Merck, Mersana, Natera, Novocure, NRG Oncology, Nuvation, Onconova, OnCusp, Pfizer, Quantus, R-Pharm, Regeneron, Seagen, Sutro Biopharma, Tesaro, Toray, and Tubulis. The terms and conditions of all these relationships are being managed in accordance with the policies and procedures of NYU Langone. For full disclosures of the other study authors, visit ctimeetingtech.com/esmo2026.
