A Phase II clinical trial led by researchers at Yale School of Medicine and Yale Cancer Center has found that the antibody-drug conjugate sacituzumab govitecan, also known as Trodelvy, demonstrated encouraging clinical activity in patients with recurrent uterine cancer who had already exhausted several standard treatment options.
The findings, published in Clinical Cancer Research, suggest the therapy could become an important new option for patients with advanced endometrial cancer after chemotherapy and immunotherapy stop working.
A difficult disease to treat after relapse
Endometrial cancer is the most common gynecologic cancer in the United States, and rates continue to rise worldwide. While recent advances in immunotherapy have improved treatment for some patients, options remain limited once the disease returns after platinum-based chemotherapy or checkpoint inhibitor therapy.
Patients with recurrent disease often face poor outcomes, particularly those with aggressive tumor types such as uterine serous carcinoma and carcinosarcoma. Standard second-line chemotherapies typically produce modest response rates and short-lived disease control.
Researchers therefore wanted to investigate whether sacituzumab govitecan could improve outcomes in this challenging setting.
How the drug works
Sacituzumab govitecan belongs to a newer class of targeted therapies known as antibody-drug conjugates, or ADCs. These drugs combine an antibody that recognizes cancer cells with a chemotherapy payload designed to destroy them.
In this case, the therapy targets Trop-2, a protein commonly overexpressed in several aggressive cancers, including many uterine tumors. Attached to the antibody is SN-38, the active metabolite of irinotecan, a well-known chemotherapy drug.
By delivering chemotherapy directly to Trop-2–expressing cancer cells, researchers hope to increase anti-tumor activity while limiting damage to healthy tissue.
The drug is already approved for metastatic breast cancer and urothelial cancer, but remains investigational in uterine cancer.
Trial included heavily pretreated patients
The study enrolled 50 patients with recurrent or persistent endometrial cancer between 2020 and 2024. All participants had previously received platinum-based chemotherapy, and many had also undergone treatment with immune checkpoint inhibitors such as pembrolizumab or dostarlimab.
The study population represented a particularly difficult-to-treat group. Most patients had aggressive tumor histologies, including serous carcinoma, carcinosarcoma, or grade 3 endometrioid disease. Patients had received a median of two prior treatment regimens, with some undergoing as many as four lines of therapy before entering the study.
Encouraging responses and survival data
The trial met its primary endpoint, achieving an objective response rate of 28%. Two patients experienced complete responses with no detectable cancer remaining, while another 12 patients achieved partial responses with substantial tumor shrinkage.
In total, more than 70% of evaluable patients experienced some degree of tumor reduction during treatment. The study also reported durable responses, with a median response duration of 9.3 months. Several patients were still responding at the time of analysis.
Median progression-free survival reached 5.5 months, while median overall survival was 17.5 months in this heavily pretreated population.
Researchers also noted that responses were observed across multiple tumor subtypes rather than being limited to one specific histology.
“The results of our Investigator Initiated Trial complement and extend the TROPiCS-03 Trial results by demonstrating significant clinical activity of SG not only against the most common histological types of uterine cancer (endometrioid tumors) but also in patients harboring biologically aggressive endometrial tumors such as uterine serous carcinoma and carcinosarcoma,” said Alessandro Santin, MD, the study’s lead author.
Side effects remained manageable
As expected with potent cancer therapies, treatment-related side effects were common. The most frequent severe toxicities included neutropenia, anemia, fatigue, diarrhea, and febrile neutropenia.
However, investigators reported that most adverse events were manageable using supportive care measures such as growth factor support, anti-diarrheal medications, hydration, and dose adjustments. No treatment-related deaths were reported during the trial.
Looking ahead
The researchers cautioned that the study was relatively small and lacked a randomized comparison arm. Nevertheless, the results add to growing evidence supporting sacituzumab govitecan in advanced endometrial cancer, particularly for patients who have limited options remaining after standard therapies fail.
A larger international Phase III study is already underway to compare the drug directly against standard chemotherapy in patients with recurrent endometrial cancer following platinum chemotherapy and immunotherapy.
The team also highlighted future possibilities for combining the therapy with immunotherapy approaches, particularly because the drug’s chemotherapy payload may help stimulate anti-tumor immune responses.
“This is a major bench-to-bedside accomplishment for patients with uterine cancer,” Santin said.
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