Next-generation drug reduces endometrial cancer progression and death in trial

A new drug is effective at decreasing the recurrence of, and death from, endometrial cancer, an international study shows. The drug, called sacituzumab tirumotecan (sac-TMT), attaches to a protein on the surface of tumor cells and then delivers a targeted dose of a chemical that leads to cancer cell death.

Cancers of the inner lining of the uterus (endometrium) are the most common in the female reproductive system. They are becoming more deadly and have few effective treatment options, especially if diagnosed late, researchers say. Moreover, until now, no standard therapies have existed to prevent or stall their recurrence after initial chemotherapy and immunotherapy.

Lower progression and death risks

Led by researchers at NYU Langone Health and its Perlmutter Cancer Center, the TroFuse-005/ENGOT-en23/GOG-3095 study compared treatment with sac-TMT to treatment with standard chemotherapy drugs in women who had already been treated with chemotherapy and then immunotherapy for advanced or recurring endometrial cancer.

All study participants had already been successfully treated with pembrolizumab (Keytruda), an established PD-1 inhibitor drug that makes cancer cells more visible to immune system attack.

Results of this Phase III trial showed that 386 women, randomly selected to be treated with sac-TMT after immunotherapy, had a 41% lower risk of their endometrial cancer progressing (growing in size and spreading to other parts of the body) than 390 endometrial cancer survivors who were treated with chemotherapy alone after immunotherapy.

Overall risk of death within the sac-TMT group was also 32% lower than in the standard chemotherapy-treated group.

More than twice as many women treated with sac-TMT showed a response, such as tumor shrinkage, than those treated with standard chemotherapy (35.1% versus 17.3%, respectively).

The most frequent side effects in the sac-TMT group were low blood counts (anemia and neutropenia), inflammation in the mouth (oral mucositis or stomatitis), and dry or itchy eyes—all of which were manageable, according to the researchers.

Initial data from the TroFuse-005/ENGOT-en23/GOG-3095 study, known formally in the United States as NCT06132958, were presented at the annual meeting of the European Society for Medical Oncology and simultaneously published online in The Lancet.

Rising deaths and unequal risks

“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, M.D., an assistant professor at NYU Grossman School of Medicine and gynecologic oncologist at Perlmutter Cancer Center.

“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,” said Lightfoot. “Antibody-drug conjugates such as sacituzumab tirumotecan are effective in targeting and treating these aggressive cancers to delay their progression and prolong survival when they recur.”

Death rates from uterine cancers in the United States, she noted, have risen to more than 14,000 annually, with an estimated 68,000 newly diagnosed cases in 2026 alone.

Implications for treatment and other cancers

“These positive results from the first Phase III trial using sacituzumab tirumotecan after immunotherapy establish this drug as a new standard treatment in recurrent endometrial cancer,” said study principal investigator and gynecologic oncologist Bhavana Pothuri, M.D., M.S.

“As a result of this practice-changing study, clinical guidelines for endometrial cancer will need to be reassessed to incorporate sacituzumab tirumotecan,” said Pothuri, a 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.

Pothuri said that effective therapies like sac-TMT are needed because the disease is increasingly common and more deadly, with poor overall survival once the cancer has spread outside the uterus.

The drug sac-TMT is designed to latch onto the trophoblast cell-surface antigen 2 (Trop-2), a protein that sits in abundance on the surface of endometrial cancer cells.

Pothuri said that the success of TroFuse-005/ENGOT-en23/GOG-3095 offers promise that sac-TMT could also serve as a therapy for other cancers in which Trop-2 is overexpressed, such as in tumors of the lungs, breasts, ovaries, and intestines.

For the TroFuse-005/ENGOT-en23/GOG-3095 trial, endometrial cancer patients were enrolled at more than 200 cancer centers in 29 countries across Europe, Asia, and North America, including in the U.S. Three patients in each treatment group died during follow-up. Most patients were monitored for at least a year after enrolling in the trial and being randomized into treatment groups.

According to the National Institutes of Health, more than 3% of American women will be diagnosed with uterine cancer during their lifetime, with 890,295 living with the disease in 2023.

Who’s behind this story?

Sadie Harley

BSc Life Sciences & Ecology. Microbiology lab background with pharmaceutical news experience in oil, gas, and renewable industries.

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Robert Egan

Bachelor’s in mathematical biology, Master’s in creative writing. Well-traveled with unique perspectives on science and language.

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