UPCC 15825 A Phase 3 Randomized, Open-label, Multicenter Study to Compare the Efficacy and Safety of Sacituzumab Tirumotecan in Combination with Pembrolizumab Versus Pembrolizumab Alone as First-line Maintenance Treatment in Participants with Mismatch Repair Proficient Endometrial Cancer (TroFuse-033/GOG-3119/ENGOT-en29) (TroFuse-033)

Study of Treatment Combinations for Advanced Endometrial Cancer

Enrolling By Invitation
18 years or above
Female
Phase 3
1123 participants needed
1 Location

Brief description of study

Researchers are looking for new ways to treat people with proficient mismatch repair (pMMR) endometrial cancer (EC) that is advanced or recurrent.

  • EC is a type of cancer that starts in the tissues inside the uterus (womb)
  • pMMR indicates that certain normal proteins are present in the cancer cells
  • Advanced means the cancer has spread locally or to other parts of the body (metastatic) and cannot be removed with surgery
  • Recurrent means the cancer came back after surgery

Sacituzumab tirumotecan (also known as sac-TMT) and pembrolizumab are the study medicines. Sac-TMT is an antibody drug conjugate (ADC). An ADC attaches to specific targets on cancer cells and delivers treatment to destroy those cells.

The goal of this study is to learn if people who receive sac-TMT with pembrolizumab live longer and without the cancer getting worse compared to people who receive pembrolizumab alone.

Detailed description of study

All participants undergo an initial Induction Phase of six cycles, each cycle consisting of pembrolizumab + carboplatin + paclitaxel or docetaxel. Each cycle is three weeks. Participants whose cancer does not progress enter the Maintenance Treatment Phase and are then randomly assigned to pembrolizumab + sac-TMT or pembrolizumab monotherapy. Participants whose cancer does progress will have the possibility to enter the Subsequent Treatment Phase and are then randomly assigned to pembrolizumab + sac-TMT or sac-TMT monotherapy.

Eligibility of study

You may be eligible for this study if you meet the following criteria:

  • Conditions: Endometrial Cancer
  • Age: 18 years or above
  • Gender: Female

Key inclusion criteria include but are not limited to:

  • Has a histologically confirmed diagnosis of primary advanced or recurrent endometrial carcinoma that has been confirmed as proficient mismatch repair (pMMR)
  • Has radiographically evaluable disease, with measurable Stage III or either measurable or non-measurable Stage IV or recurrent disease per Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST 1.1), as assessed by the investigator
  • Has received no prior systemic therapy for endometrial carcinoma except the following conditions as pre-specified by the protocol: 1 prior line of systemic platinum-based adjuvant and/or neoadjuvant chemotherapy in the setting of curative-intent, prior radiation with or without radiosensitizing chemotherapy if >2 weeks before the start of induction treatment, or prior hormonal therapy for treatment of endometrial carcinoma that was discontinued ≥1 week before the start of induction treatment

Key exclusion criteria include but are not limited to:

  • Has carcinosarcoma, neuroendocrine tumors or endometrial sarcoma, including stromal sarcoma, leiomyosarcoma, adenosarcoma, or other types of sarcomas
  • Has endometrial carcinoma of any histology that is mismatch repair deficient (dMMR)
  • Is a candidate for debulking surgery resulting in complete removal of all tumor and no evidence of radiological disease following surgery, or curative-intent radiotherapy at the time of enrollment
  • Has a history of documented severe dry eye syndrome, severe Meibomian gland disease and/or blepharitis, or severe corneal disease that prevents/delays corneal healing
  • Has active inflammatory bowel disease requiring immunosuppressive medication or previous history of inflammatory bowel disease
  • Has uncontrolled, significant cardiovascular disease or cerebrovascular disease
  • Human Immunodeficiency Virus-infected participants with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease
  • Received prior therapy in any setting with any of the following: anti-programmed cell death 1 protein, anti-programmed cell death ligand 1, anti-programmed cell death ligand 2 agent, or with an agent directed to another stimulatory or coinhibitory T-cell receptor; trophoblast cell surface antigen 2-targeted antibody drug conjugate; or topoisomerase I inhibitor-containing antibody drug conjugate

This study investigates the treatment of advanced or recurrent endometrial cancer with proficient mismatch repair (pMMR). In pMMR endometrial cancer, certain normal proteins are present in the cancer cells. This condition can be advanced, meaning the cancer has spread beyond the uterus, or recurrent, meaning it has returned after treatment. The purpose of this study is to compare the effectiveness of a combination of investigational medications, including an antibody drug conjugate (ADC) called sacituzumab tirumotecan (sac-TMT) and pembrolizumab, against pembrolizumab alone.

Participants will initially receive six cycles of induction treatment with pembrolizumab, carboplatin, and either paclitaxel or docetaxel. Each cycle lasts three weeks. If the cancer does not progress, participants will enter the Maintenance Treatment Phase, where they will be randomly assigned to receive either pembrolizumab with sac-TMT or pembrolizumab alone. If the cancer progresses, participants may enter the Subsequent Treatment Phase and receive either pembrolizumab with sac-TMT or sac-TMT alone.

  • Who can participate: Participants must have advanced or recurrent endometrial cancer confirmed as proficient mismatch repair (pMMR) and measurable disease. Prior systemic therapy for endometrial carcinoma is not allowed, except under specific conditions outlined in the study protocol.
  • Study details: The study begins with an induction phase of six treatment cycles. If the cancer does not progress, participants proceed to a maintenance phase with randomly assigned treatment combinations.
Updated on 27 Jul 2026. Study ID: 25-0609
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