Clinical trial NCT06952504: 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)
Official title: 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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Endometrial Cancer
Keywords: Programmed Cell Death-1 (PD1, PD-1)
Programmed Cell Death 1 Ligand 1 (PDL1, PD-L1)
Programmed Cell Death 1 Ligand 2 (PDL2, PD-L2)
Trophoblast cell surface antigen 2 (TROP2)
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2025-05-01
Enrollment: 1123
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
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

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 + 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 criteria: 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 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

Primary outcomes:
measure: Maintenance Treatment: Progression-Free Survival (PFS)
timeFrame: Up to approximately 44 months
measure: Maintenance Treatment: Overall Survival (OS)
timeFrame: Up to approximately 54 months
Secondary outcomes:
measure: Maintenance Treatment: Progression-Free Survival 2 (PFS2) as Assessed by Investigator
timeFrame: Up to approximately 54 months
measure: Maintenance Treatment: Number of Participants Who Experience One or More Adverse Events (AEs)
timeFrame: Up to approximately 27 months
measure: Maintenance Treatment: Number of Participants Who Discontinue Study Intervention Due to an AE
timeFrame: Up to approximately 24 months
measure: 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 (Item 29) and Quality of Life (Item 30) Item Mean Score
timeFrame: Baseline and up to approximately 24 months
measure: Maintenance Treatment: Change from baseline in EORTC QLQ-C30 Physical Functioning (Items 1-5) Combined Score
timeFrame: Baseline and up to approximately 24 months
measure: Maintenance Treatment: Change from baseline in EORTC QLQ-C30 Role Functioning (Items 6 and 7) Combined Score
timeFrame: Baseline and up to approximately 24 months
measure: Maintenance Treatment: Change from baseline in EORTC QLQ Endometrial Cancer Symptom Score (QLQ-EN24)
timeFrame: Baseline and up to approximately 24 months
Other outcomes:
Locations:
city: Miami Beach
country: United States
facility: Mount Sinai Cancer Center ( Site 6031)
state: Florida
city: Shreveport
country: United States
facility: TRIALS 365 ( Site 6005)
state: Louisiana
city: Haifa
country: Israel
facility: Rambam Health Care Campus ( Site 2025)
city: Haifa
country: Israel
facility: Carmel Hospital ( Site 2023)
city: Jerusalem
country: Israel
facility: Shaare Zedek Medical Center ( Site 2020)
city: Tel Aviv
country: Israel
facility: Sourasky Medical Center ( Site 2022)
city: San Juan
country: Puerto Rico
facility: Puerto Rico Cancer Specialists Clinical Trials ( Site 4201)
city: Taoyuan
country: Taiwan
facility: Linkou Chang Gung Memorial Hospital ( Site 3705)
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References: