Endometrial Cancer
Conditions
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)
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.
Interventions
BIOLOGICALPembrolizumab
Intravenous (IV) Infusion
DRUGCarboplatin
During the Induction Phase, participants receive carboplatin AUC 5 (mg/mL/min) on Day 1 of each 3-week cycle for 6 cycles (up to approximately 4 months) via IV infusion.
DRUGPaclitaxel
During the Induction Phase, participants receive paclitaxel 175 mg/m\^2 on Day 1 of each 3-week cycle for 6 cycles (up to approximately 4 months) via IV infusion.
DRUGDocetaxel
During the Induction Phase, participants may receive docetaxel (in place of paclitaxel) 75 mg/m\^2 on Day 1 of each 3-week cycle for 6 cycles (up to approximately 4 months) via IV infusion.
BIOLOGICALSacituzumab Tirumotecan
IV Infusion
DRUGCisplatin
During the Induction Phase, participants may receive cisplatin (in place of carboplatin) 75 mg/m\^2 on Day 1 of each 3-week cycle for 6 cycles (up to approximately 4 months) via IV infusion
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
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.
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion 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 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maintenance Treatment: Progression-Free Survival (PFS) | 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. |
| Maintenance Treatment: Overall Survival (OS) | Up to approximately 54 months | OS is defined as time from randomization to death due to any cause. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maintenance Treatment: Progression-Free Survival 2 (PFS2) as Assessed by Investigator | Up to approximately 54 months | 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. |
| Maintenance Treatment: Number of Participants Who Experience One or More Adverse Events (AEs) | Up to approximately 27 months | 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. |
| Maintenance Treatment: Number of Participants Who Discontinue Study Intervention Due to an AE | Up to approximately 24 months | 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. |
| 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 | 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 Global Health Status/Quality of Life score (Items 29 and 30) will be presented. |
| Maintenance Treatment: Change from baseline in EORTC QLQ-C30 Physical Functioning (Items 1-5) Combined Score | Baseline and up to approximately 24 months | 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. |
| Maintenance Treatment: Change from baseline in EORTC QLQ-C30 Role Functioning (Items 6 and 7) Combined Score | Baseline and up to approximately 24 months | 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. |
| Maintenance Treatment: Change from baseline in EORTC QLQ-EN24 Symptom Score | Baseline and up to approximately 24 months | 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 reflects greater symptom severity. The change from baseline in EORTC QLQ-EN24 back and pelvis pain score will be presented. |
Countries
Argentina, Australia, Austria, Belgium, Brazil, Canada, Chile, China, Colombia, Czechia, Denmark, Finland, France, Germany, Greece, Hungary, Ireland, Israel, Italy, Japan, Mexico, Netherlands, Norway, Peru, Poland, Puerto Rico, Singapore, South Korea, Spain, Sweden, Taiwan, Thailand, United Kingdom, United States
Contacts
CONTACTToll Free Number
STUDY_DIRECTORMedical Director
Merck Sharp & Dohme LLC
Outcome results
None listed