A Phase 3 Randomized, Open-label, Multicenter Study to Compare the Efficacy and Safety of Sacituzumab Tirumotecan (Sac-TMT, MK-2870) 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)
Trial Snapshot
- Phase
- Phase 3
- Status
- Recruiting
- Sponsor
- Merck Sharp & Dohme LLC
- Enrollment
- 1,123
- Locations
- 471
- Primary Endpoint
- Maintenance Treatment: Overall Survival (OS)
Study Overview
Brief Summary
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
All participants undergo an initial Induction Phase of six cycles, each cycle consisting of pembrolizumab + carboplatin or cisplatin + 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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Single (Outcomes Assessor)
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- 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 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
Arms & Interventions
Subsequent Treatment Arm B: Sacituzumab Tirumotecan Monotherapy
During the Induction Phase, participants receive pembrolizumab 200 mg, carboplatin AUC 5 (mg/mL/min) or cisplatin 75 mg/m^2, and paclitaxel 175 mg/m^2 or docetaxel 75 mg/m^2 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.
Intervention: Carboplatin (Drug)
Subsequent Treatment Arm A: Pembrolizumab + Sacituzumab Tirumotecan
During the Induction Phase, participants receive pembrolizumab 200 mg, carboplatin AUC 5 (mg/mL/min) or cisplatin 75 mg/m^2, and paclitaxel 175 mg/m^2 or docetaxel 75 mg/m^2 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).
Intervention: Paclitaxel (Drug)
Subsequent Treatment Arm A: Pembrolizumab + Sacituzumab Tirumotecan
During the Induction Phase, participants receive pembrolizumab 200 mg, carboplatin AUC 5 (mg/mL/min) or cisplatin 75 mg/m^2, and paclitaxel 175 mg/m^2 or docetaxel 75 mg/m^2 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).
Intervention: Sacituzumab Tirumotecan (Biological)
Subsequent Treatment Arm B: Sacituzumab Tirumotecan Monotherapy
During the Induction Phase, participants receive pembrolizumab 200 mg, carboplatin AUC 5 (mg/mL/min) or cisplatin 75 mg/m^2, and paclitaxel 175 mg/m^2 or docetaxel 75 mg/m^2 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.
Intervention: Sacituzumab Tirumotecan (Biological)
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) or cisplatin 75 mg/m^2, and paclitaxel 175 mg/m^2 or docetaxel 75 mg/m^2 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).
Intervention: Cisplatin (Drug)
Subsequent Treatment Arm B: Sacituzumab Tirumotecan Monotherapy
During the Induction Phase, participants receive pembrolizumab 200 mg, carboplatin AUC 5 (mg/mL/min) or cisplatin 75 mg/m^2, and paclitaxel 175 mg/m^2 or docetaxel 75 mg/m^2 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.
Intervention: Cisplatin (Drug)
Subsequent Treatment Arm A: Pembrolizumab + Sacituzumab Tirumotecan
During the Induction Phase, participants receive pembrolizumab 200 mg, carboplatin AUC 5 (mg/mL/min) or cisplatin 75 mg/m^2, and paclitaxel 175 mg/m^2 or docetaxel 75 mg/m^2 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).
Intervention: Carboplatin (Drug)
Subsequent Treatment Arm B: Sacituzumab Tirumotecan Monotherapy
During the Induction Phase, participants receive pembrolizumab 200 mg, carboplatin AUC 5 (mg/mL/min) or cisplatin 75 mg/m^2, and paclitaxel 175 mg/m^2 or docetaxel 75 mg/m^2 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.
Intervention: Docetaxel (Drug)
Maintenance Treatment Arm B: Pembrolizumab Monotherapy
During the Induction Phase, participants receive pembrolizumab 200 mg, carboplatin AUC 5 (mg/mL/min) or cisplatin 75 mg/m^2, and paclitaxel 175 mg/m^2 or docetaxel 75 mg/m^2 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).
Intervention: Cisplatin (Drug)
Maintenance Treatment Arm B: Pembrolizumab Monotherapy
During the Induction Phase, participants receive pembrolizumab 200 mg, carboplatin AUC 5 (mg/mL/min) or cisplatin 75 mg/m^2, and paclitaxel 175 mg/m^2 or docetaxel 75 mg/m^2 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).
Intervention: Docetaxel (Drug)
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) or cisplatin 75 mg/m^2, and paclitaxel 175 mg/m^2 or docetaxel 75 mg/m^2 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).
Intervention: Paclitaxel (Drug)
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) or cisplatin 75 mg/m^2, and paclitaxel 175 mg/m^2 or docetaxel 75 mg/m^2 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).
Intervention: Docetaxel (Drug)
Subsequent Treatment Arm A: Pembrolizumab + Sacituzumab Tirumotecan
During the Induction Phase, participants receive pembrolizumab 200 mg, carboplatin AUC 5 (mg/mL/min) or cisplatin 75 mg/m^2, and paclitaxel 175 mg/m^2 or docetaxel 75 mg/m^2 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).
Intervention: Pembrolizumab (Biological)
Subsequent Treatment Arm A: Pembrolizumab + Sacituzumab Tirumotecan
During the Induction Phase, participants receive pembrolizumab 200 mg, carboplatin AUC 5 (mg/mL/min) or cisplatin 75 mg/m^2, and paclitaxel 175 mg/m^2 or docetaxel 75 mg/m^2 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).
Intervention: Docetaxel (Drug)
Subsequent Treatment Arm A: Pembrolizumab + Sacituzumab Tirumotecan
During the Induction Phase, participants receive pembrolizumab 200 mg, carboplatin AUC 5 (mg/mL/min) or cisplatin 75 mg/m^2, and paclitaxel 175 mg/m^2 or docetaxel 75 mg/m^2 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).
Intervention: Cisplatin (Drug)
Maintenance Treatment Arm B: Pembrolizumab Monotherapy
During the Induction Phase, participants receive pembrolizumab 200 mg, carboplatin AUC 5 (mg/mL/min) or cisplatin 75 mg/m^2, and paclitaxel 175 mg/m^2 or docetaxel 75 mg/m^2 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).
Intervention: Paclitaxel (Drug)
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) or cisplatin 75 mg/m^2, and paclitaxel 175 mg/m^2 or docetaxel 75 mg/m^2 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).
Intervention: Carboplatin (Drug)
Subsequent Treatment Arm B: Sacituzumab Tirumotecan Monotherapy
During the Induction Phase, participants receive pembrolizumab 200 mg, carboplatin AUC 5 (mg/mL/min) or cisplatin 75 mg/m^2, and paclitaxel 175 mg/m^2 or docetaxel 75 mg/m^2 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.
Intervention: Paclitaxel (Drug)
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) or cisplatin 75 mg/m^2, and paclitaxel 175 mg/m^2 or docetaxel 75 mg/m^2 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).
Intervention: Pembrolizumab (Biological)
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) or cisplatin 75 mg/m^2, and paclitaxel 175 mg/m^2 or docetaxel 75 mg/m^2 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).
Intervention: Sacituzumab Tirumotecan (Biological)
Maintenance Treatment Arm B: Pembrolizumab Monotherapy
During the Induction Phase, participants receive pembrolizumab 200 mg, carboplatin AUC 5 (mg/mL/min) or cisplatin 75 mg/m^2, and paclitaxel 175 mg/m^2 or docetaxel 75 mg/m^2 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).
Intervention: Carboplatin (Drug)
Maintenance Treatment Arm B: Pembrolizumab Monotherapy
During the Induction Phase, participants receive pembrolizumab 200 mg, carboplatin AUC 5 (mg/mL/min) or cisplatin 75 mg/m^2, and paclitaxel 175 mg/m^2 or docetaxel 75 mg/m^2 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).
Intervention: Pembrolizumab (Biological)
Outcomes
Primary Outcomes
Maintenance Treatment: Overall Survival (OS)
Time Frame: Up to approximately 54 months
OS is defined as time from randomization to death due to any cause.
Maintenance Treatment: Progression-Free Survival (PFS)
Time Frame: Up to approximately 44 months
PFS is defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurs first as assessed by Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as evaluated by the blinded independent central review (BICR). PD is defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions is also considered PD.
Secondary Outcomes
- Maintenance Treatment: Progression-Free Survival 2 (PFS2) as Assessed by Investigator(Up to approximately 54 months)
- Maintenance Treatment: Number of Participants Who Discontinue Study Intervention Due to an AE(Up to approximately 24 months)
- Maintenance Treatment: Change from baseline in EORTC QLQ-C30 Physical Functioning (Items 1-5) Combined Score(Baseline and up to approximately 24 months)
- Maintenance Treatment: Number of Participants Who Experience One or More Adverse Events (AEs)(Up to approximately 27 months)
- Maintenance Treatment: Change from baseline in EORTC QLQ-C30 Role Functioning (Items 6 and 7) Combined Score(Baseline and up to approximately 24 months)
- Maintenance Treatment: Change from baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Global Health Status/Quality of Life (Items 29 and 30) Mean Score(Baseline and up to approximately 24 months)
- Maintenance Treatment: Change from baseline in EORTC QLQ-EN24 Symptom Score(Baseline and up to approximately 24 months)