Treating Recurrent dMMR or MSI-High Endometrial Cancer with the Immunotherapy Drug, Nivolumab with or without the Immunotherapy Drug, Ipilimumab

About The Study

This clinical trial is studying two different immunotherapy approaches for people with endometrial cancer that has come back after treatment (recurrent). It focuses on tumors that have a biomarker called mismatch repair deficiency, (dMMR or MMR-D) or microsite instability high (MSI-High). These biomarkers are often found in cancers that respond to immunotherapy.

Researchers want to see whether giving the immunotherapy nivolumab (Opdivo) together with a second immunotherapy called ipilimumab (Yervoy) works better to shrink tumors and delay the cancer’s return than giving nivolumab by itself. Both nivolumab and ipilimumab are immunotherapy drugs that help the immune system recognize and attack cancer cells.

What the Study Involves

If a person joins this study, they will be randomly placed into one of two groups:

• Group 1: Receive nivolumab combined with ipilimumab.

• Group 2: Receive nivolumab alone.

Treatment is given through intravenous (IV) infusions at scheduled intervals. Some participants may also have tissue and blood samples collected, as well as imaging studies like CT or MRI, to monitor the cancer.

Participants will continue treatment until the cancer progresses, side effects become unacceptable, or they complete the planned treatment. After treatment, participants are followed regularly to check their health and monitor cancer outcomes.

People with the following may be eligible:

• diagnosed with recurrent endometrial cancer whose tumors have a biomarker called deficient mismatch repair (dMMR or MMR-D).
• participants may have received previous treatments, including:
  • one or two prior chemotherapy treatments.
  • prior immunotherapy (anti-PD-1 or anti-PD-L1) that was given in combination with chemotherapy or radiation, the cancer initially responded fully, and it returned at least 12 months after the last immunotherapy dose. 
  • prior radiation therapy for endometrial cancer, as long as radiation ended at least 4 weeks before joining the study.  
  • prior hormonal therapy for endometrial cancer, as long as the hormonal treatment was stopped at least 3 weeks before joining the study. 

People cannot join the study if they: 

• do not have recurrent endometrial cancer.
• have a subtype of endometrial cancer called serous carcinoma or carcinosarcoma.
• their cancer is mismatch repair proficient (pMMR or MMR-P) and microsatellite stable (MSS). 
• have received previous treatment with a type of immunotherapy known as a CTLA-4 inhibitor.