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)

Phase 3RecruitingNCT06952504

Merck Sharp & Dohme LLC1,123 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

SINGLE

Enrollment

1,123

Conditions

Endometrial Cancer

Eligibility

Sex: FEMALEMin age: 18 Years

Medical Language ↔ Plain English

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 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

Outcomes

Primary Outcomes

Maintenance Treatment: Progression-Free Survival (PFS)

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.

Time frame: Up to approximately 44 months

Maintenance Treatment: Overall Survival (OS)

OS is defined as time from randomization to death due to any cause.

Time frame: Up to approximately 54 months

Secondary Outcomes

Maintenance Treatment: Progression-Free Survival 2 (PFS2) as Assessed by Investigator

PFS2 is defined as the time from randomization to the documented subsequent objective disease progression after initiation of new anticancer therapy or death due to any cause, whichever occurs first. PFS2 as assessed by the investigator will be presented.

Time frame: Up to approximately 54 months

Maintenance Treatment: Number of Participants Who Experience One or More Adverse Events (AEs)

An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.

Time frame: Up to approximately 27 months

Maintenance Treatment: Number of Participants Who Discontinue Study Intervention Due to an AE

An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.

Time frame: 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 (Item 29) and Quality of Life (Item 30) Item Mean Score

EORTC QLQ-C30 is a 30-item scale to assess the overall quality of life of cancer patients. Participant responses to the questions "How would you rate your overall health during the past week?" and "How would you rate your overall quality of life during the past week?" are scored on a 7- point scale (1= Very poor to 7=Excellent). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. A higher score indicates a better overall health status. The change from baseline in EORTC QLQ-C30 Items 29 and 30 mean score will be presented.

Time frame: Baseline and up to approximately 24 months

Maintenance Treatment: Change from baseline in EORTC QLQ-C30 Physical Functioning (Items 1-5) Combined Score

EORTC QLQ-C30 is a 30-item scale to assess the overall quality of life of cancer patients. The physical functioning score is based on participant responses to questions scored on a 4-point scale (1 = 'Not at All' to 4 = 'Very Much'). Higher scores indicate better physical functioning. The change from baseline in EORTC QLQ-C30 Physical Functioning (Items 1-5) combined score will be presented.

Time frame: Baseline and up to approximately 24 months

Maintenance Treatment: Change from baseline in EORTC QLQ-C30 Role Functioning (Items 6 and 7) Combined Score

EORTC QLQ-C30 is a 30-item scale to assess the overall quality of life of cancer patients. The role functioning score is based on participant responses to questions scored on a 4-point scale (1 = 'Not at All' to 4 = 'Very Much'). Higher scores indicate better role functioning. The change from baseline in EORTC QLQ-C30 Role Functioning (Items 6 and 7) combined score will be presented.

Time frame: Baseline and up to approximately 24 months

Maintenance Treatment: Change from baseline in EORTC QLQ Endometrial Cancer Symptom Score (QLQ-EN24)

The EORTC-QLQ-EN24 is a 24-item questionnaire developed to be used in conjunction with the EORTC-QLQ-C30 to assess the quality of life of endometrial cancer patients. Participant responses are scored on a 4-point scale (1=not at all to 4=very much). A higher score indicates a better quality of life. The change from baseline in EORTC QLQ-E24 back and pelvis pain score will be presented.

Time frame: Baseline and up to approximately 24 months

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)

Overview

Conditions

Interventions

Eligibility

Locations (220)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts