A Study to Compare Sacituzumab Tirumotecan (MK-2870) in Combination With Pembrolizumab (MK-3475) Versus Pembrolizumab Alone as Treatment in Participants With Mismatch Repair Proficient Endometrial Cancer (MK-2870-033/TroFuse-033/GOG-3119/ENGOT-en29)
Purpose
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.
Condition
- Endometrial Cancer
Eligibility
- Eligible Ages
- Over 18 Years
- Eligible Genders
- Female
- Accepts Healthy Volunteers
- No
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
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 curative-intent 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 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
Study Design
- Phase
- Phase 3
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel Assignment
- Intervention Model Description
- Participants are allocated to a single induction arm, then assigned randomly to either one of two maintenance treatment arms or one of two subsequent treatment arms.
- Primary Purpose
- Treatment
- Masking
- Single (Outcomes Assessor)
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Experimental Maintenance Treatment Arm A: Pembrolizumab + Sacituzumab Tirumotecan |
During the Induction Phase, participants receive pembrolizumab 200 mg, carboplatin area under the curve (AUC) 5 (mg/mL/min), and paclitaxel 175 mg/m2 or docetaxel 75 mg/m2 on Day 1 of each 3-week cycle for 6 cycles (up to approximately 4 months). During the Maintenance Treatment Phase, participants receive sac-TMT 4 mg/kg on Days 1, 15, and 29 of each 6-week cycle and pembrolizumab 400 mg on Day 1 of each 6-week cycle for up to 14 cycles (up to approximately 19 months). |
|
|
Active Comparator Maintenance Treatment Arm B: Pembrolizumab Monotherapy |
During the Induction Phase, participants receive pembrolizumab 200 mg, carboplatin AUC 5 (mg/mL/min), and paclitaxel 175 mg/m2 or docetaxel 75 mg/m2 on Day 1 of each 3-week cycle for 6 cycles (up to approximately 4 months). During the Maintenance Treatment Phase, participants receive pembrolizumab 400 mg on Day 1 of each 6-week cycle for up to 14 cycles (up to approximately 19 months). |
|
|
Experimental Subsequent Treatment Arm A: Pembrolizumab + Sacituzumab Tirumotecan |
During the Induction Phase, participants receive pembrolizumab 200 mg, carboplatin AUC 5 (mg/mL/min), and paclitaxel 175 mg/m2 or docetaxel 75 mg/m2 on Day 1 of each 3-week cycle for 6 cycles (up to approximately 4 months). During the Subsequent Treatment Phase, participants receive sac-TMT 4 mg/kg on Days 1, 15, and 29 of each 6-week cycle until discontinuation criteria is met and pembrolizumab 400 mg on Day 1 of each 6-week cycle for up to 14 cycles (up to approximately 19 months). |
|
|
Active Comparator Subsequent Treatment Arm B: Sacituzumab Tirumotecan Monotherapy |
During the Induction Phase, participants receive pembrolizumab 200 mg, carboplatin AUC 5 (mg/mL/min), and paclitaxel 175 mg/m2 or docetaxel 75 mg/m2 on Day 1 of each 3-week cycle for 6 cycles (up to approximately 4 months). During the Subsequent Treatment Phase, participants receive sac-TMT 4 mg/kg on Days 1, 15, and 29 of each 6-week cycle until discontinuation criteria is met. |
|
Recruiting Locations
Miami Beach, Florida 33140
Brian Slomovitz
305-243-2233
San Juan, Puerto Rico 00917
Luis Santos-Reyes
787-407-3797
More Details
- NCT ID
- NCT06952504
- Status
- Recruiting
- Sponsor
- Merck Sharp & Dohme LLC
Detailed Description
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.