- Sacituzumab tirumotecan (sac-TMT) was associated with a 41% lower risk of endometrial cancer progression compared with standard chemotherapy in females previously treated with chemotherapy and immunotherapy.
- Those receiving sac-TMT also had a 32% lower risk of death than those receiving standard chemotherapy.
- More than twice as many women treated with sac-TMT experienced a response, such as tumor shrinkage, compared with chemotherapy (35.1% versus 17.3%).
- The findings suggest sac-TMT could offer a promising new treatment option for people with advanced or recurrent endometrial cancer, although further evaluation and regulatory assessment are important.
Endometrial cancer develops in the endometrium, the inner lining of the uterus. It is the
Although the disease is
Now, the results of a phase 3 clinical trial, presented at the European Society for Medical Oncology’s annual meeting and published in The Lancet, suggest a new targeted cancer drug may help reduce the risk of disease progression and death in females with advanced or recurrent endometrial cancer.
The drug, called sacituzumab tirumotecan (sac-TMT), was associated with a 41% lower risk of cancer progression and a 32% lower risk of death compared with standard chemotherapy in women whose cancer had previously been treated with chemotherapy and immunotherapy.
The findings could offer a new treatment option for people with endometrial cancer, particularly those whose disease returns or progresses after initial treatment.
How does the new cancer drug work?
Sac-TMT belongs to a class of medications known as antibody-drug conjugates (ADCs). These treatments combine an antibody, which recognizes a specific target on cancer cells, with a drug designed to kill them.
Sac-TMT targets a protein called trophoblast cell-surface antigen 2 (Trop-2), which is found in high amounts on the surface of many endometrial cancer cells. After binding to Trop-2, the drug delivers a cancer-killing chemical to the targeted cells. This approach aims to direct treatment toward cancer cells while limiting exposure to other cells.
“Sac-TMT joins an antibody that targets TROP2 to a topoisomerase I inhibitor payload through a unique bifunctional linker. The linker is designed to stay stable in the bloodstream and release the payload inside tumor cells after the drug binds TROP2 and is internalized,” study author Domenica Lorusso, MD, PhD, at Humanitas University in Milan, Italy, explained to Medical News Today.
“The released payload stops the cancer cell from dividing and causes cell death. It can also spread to nearby tumor cells, which is known as a bystander effect,” Lorusso explained.
“TROP2 is a promising target because it is overexpressed in more than 90% of endometrial cancers, across most histologies, and it helps drive tumor growth and spread. In TroFuse-005, 98% of patients had tumors with TROP2 expression,” she continued.
The researchers investigated whether sac-TMT could help control endometrial cancer in females who had already received chemotherapy followed by Keytruda (pembrolizumab), an immunotherapy drug that helps the immune system recognize and attack cancer cells.
Until now, treatment options for people whose endometrial cancer returns or progresses after these therapies have been limited.
What did the clinical trial find?
The TroFuse-005/ENGOT-en23/GOG-3095 trial included 776 women with advanced or recurrent endometrial cancer who had previously received chemotherapy and immunotherapy.
The study enrolled participants at more than 200 cancer centers across 29 countries in Europe, Asia, and North America. Researchers randomly assigned 386 participants to receive sac-TMT and 390 to receive standard chemotherapy.
The trial found that individuals treated with sac-TMT had a 41% lower risk of disease progression than those who received chemotherapy alone. The risk of death was also 32% lower in the sac-TMT group compared with the standard chemotherapy group.
“These results are highly significant,” Lorusso emphasized to MNT. “Endometrial cancer is one of the few cancers where both incidence and mortality are rising worldwide. Immunotherapy combined with platinum chemotherapy is now standard first-line treatment, so a growing number of women will progress after both therapies. These women have a median survival of less than a year with current options.”
“TroFuse-005 is the first global Phase 3 trial, and sac-TMT is the first ADC, to show a statistically significant improvement in both OS and PFS over chemotherapy for these patients. Based on these data, the US FDA has accepted the Biologics License Application for priority review.”
– Domenica Lorusso, MD, PhD
“The most important finding is that sac-TMT met all three endpoints: overall survival (OS), progression-free survival (PFS) and objective response rate (ORR),” Lorusso highlighted to MNT.
“Most importantly, it extended overall survival. Sac-TMT reduced the risk of death by 32% (HR 0.68), with median OS of 19.0 months compared with 12.1 months for chemotherapy. That is an improvement of almost 7 months. It also reduced the risk of progression or death by 41% (HR 0.59) and doubled the response rate (35.1% vs. 17.3%),” she told us.
“The benefit was also durable,” the study author added. “Median duration of response was 11.1 months with sac-TMT versus 6.9 months with chemotherapy. Patients stayed on sac-TMT about twice as long as on chemotherapy (median 31.1 vs. 15.0 weeks). Even so, discontinuation due to treatment-related adverse events was low: 3.1% with sac-TMT compared with 4.9% with chemotherapy. Health-related quality of life was maintained over time.”
“Together, these results show that patients stayed on sac-TMT to realize a large survival benefit,” said Lorusso.
The most frequently reported side effects associated with sac-TMT included anemia, neutropenia, inflammation of the mouth, and dry or itchy eyes, which the researchers reported as manageable.
However, further assessment of the treatment’s safety, including its longer-term effects, will be important as researchers continue to evaluate its potential role in cancer care.
Why are these findings important?
Endometrial cancer remains a growing health concern, with projections suggesting that the incidence and mortality will substantially increase over the next three decades.
Therefore, ADC treatments, such as sac-TMT, could help delay cancer progression and extend survival in people whose disease returns. The drug may also represent an important advance for people who have few effective treatment options after chemotherapy and immunotherapy.
“For most patients whose cancer progresses after platinum chemotherapy and immunotherapy, the main option today is single-agent chemotherapy, such as doxorubicin or paclitaxel. There is no established standard of care,” Lorusso noted.
“These patients have historically lived less than a year after progression. In TroFuse-005, patients in the chemotherapy arm had a median OS of 12.1 months, which is consistent with prior studies of single-agent chemotherapy in this setting. With sac-TMT, median OS reached 19.0 months, and responses were twice as frequent and lasted longer,” she explained.
Additionally, sac-TMT’s potential applications may extend beyond endometrial cancer. Because the drug targets Trop-2, it may also be relevant to other cancers in which this protein is overexpressed, such as breast, prostate, pancreatic, and ovarian cancers.
However, additional clinical studies would be necessary to establish whether sac-TMT is safe and effective for other cancer types.
Similarly, although the phase 3 findings are promising, further research and regulatory assessment will help determine how sac-TMT could be incorporated into routine endometrial cancer care.
Still, the trial provides evidence that targeting Trop-2 may improve outcomes for females whose endometrial cancer has progressed or returned after previous treatment, potentially representing a meaningful step toward expanding treatment options for a disease that can be challenging to manage.
