D070 Endometrium Endometrium
Conditions
Interventions
Pembrolizumab (MK-3475): Solution, unit dose strength 25 mg/mL. Dosage levels 200 mg using a 30-minute IV infusion on day 1 of each 3-week cycle for 6 cycles. Background Treatment Drugs: Carboplatin (
Participants May Be Eligible for Second Course (9 additional cycles). Rescue medications: H1 Receptor Antagonist, H2 Receptor Antagonist, Acetaminophen (or Equivalent) (unassigned dose formulation, do
Sponsors
Merck Sharp & Dohme LLC., (una subsidiaria de Merck & Co. Inc.)
Eligibility
Sex/Gender
Female
Inclusion criteria
Inclusion criteria: An ECOG performance status of 0 to 1 assessed within 7 days before allocation to Induction. Adequate organ function as defined in the following table (Table 1). Specimens must be collected within 7 days before allocation to Induction. Criteria for All Participants Before Randomization to Either Maintenance or Subsequent Treatment Parts of the Study Has an ECOG PS of 0 or 1 as assessed at the Prerandomization Visit (most recent assessment within the visit). Type of Participant and Disease Characteristics The participant must have a histologically confirmed diagnosis of primary advanced or recurrent endometrial carcinoma that has been confirmed as pMMR by local pathology. Note: The local pMMR assay by immunohistochemistry should assess MSH6, PMS2, MSH2, and MLH1. pMMR is defined as all 4 proteins expressed. Has radiographically evaluable disease, with measurable Stage III or either measurable or non-measurable Stage IV or recurrent disease per RECIST 1.1, as assessed by the investigator. Lesions situated in a previously irradiated area are considered measurable if progression has been shown in such lesions. Note: Participants with fluid-only disease (eg, pleural effusion or ascites, and no other radiographically apparent lesions) must have cytologic confirmation of malignancy. Prior Therapy Has received no prior systemic therapy for endometrial carcinoma except as noted below: • May have received 1 prior line of systemic platinum-based adjuvant and/or neoadjuvant chemotherapy in the setting of curative-intent. This prior chemotherapy may have been given as treatment involving chemotherapy alone, concurrent chemoradiation, or as part of a sequential approach such as in a regimen involving concurrent chemoradiation followed by chemotherapy. - Instances in which both adjuvant and neoadjuvant systemic platinum-based chemotherapy are used will be counted as one line of chemotherapy. • May have received prior radiation with or without radiosensitizing chemotherapy if >2 weeks before the start of induction treatment (see also Section 5.2). Participants must have recovered adequately from all radiation-related toxicities (as determined by the investigator), not require systemic corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (=2 weeks of radiotherapy) to non-CNS disease. • May have received prior hormonal therapy for treatment of endometrial carcinoma, provided that it was discontinued =1 week before the start of induction treatment. Demographics Is assigned female sex at birth, at least 18 years of age, at the time of providing the informed consent. Follow local regulatory requirements if the legal age of consent for participation is >18 years of age. Assigned Female Sex at Birth A participant assigned female sex at birth is eligible to participate if not breastfeeding during the study intervention period and for at least 120 days after the last dose of study intervention. A POCBP is eligible to participate if not pregnant and if a negative highly sensitive pregnancy test (urine or serum), as required by local regulations, has been obtained within 24 hours (for a urine test) or 72 hours (for a serum test) before the first dose of study intervention. If a urine test cannot be confirmed as negative (eg, an ambiguous result), a serum pregnancy test is required. Additional requirements for pregnancy testing during and after study intervention are in Section 8.3.5. A POCBP is eligible to
Exclusion criteria
Exclusion criteria: Medical Conditions Has carcinosarcoma, neuroendocrine tumors or endometrial sarcoma, including stromal sarcoma, leiomyosarcoma, adenosarcoma, or other types of sarcomas. Is known to have a POLE mutation. Has endometrial carcinoma of any histology that is dMMR. Is a candidate for curative-intent surgery or curative-intent radiotherapy at the time of enrollment. Has Grade =2 peripheral neuropathy. 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 (eg, Crohn’s disease, ulcerative colitis, or chronic diarrhea). Has uncontrolled, significant cardiovascular disease or cerebrovascular disease including New York Heart Association Class III or IV congestive heart failure, unstable angina, myocardial infarction, uncontrolled symptomatic arrhythmia, prolongation of QTcF interval to >480 ms, and/or other serious cardiovascular and cerebrovascular diseases within 6 months before the start of induction treatment. HIV-infected participants with a history of Kaposi’s sarcoma and/or Multicentric Castleman’s Disease. Prior/Concomitant Therapy Received prior systemic anticancer therapy, including investigational agents, for endometrial carcinoma. Note: Prior chemotherapy administered as adjuvant therapy, neoadjuvant therapy, and/or concurrently with radiation is permitted; see Section 5.1. Received prior therapy in any setting with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent, or with an agent directed to another stimulatory or coinhibitory T-cell receptor (eg, CTLA-4, OX-40, CD137). Received prior treatment with a TROP2-targeted ADC. Received prior treatment with a topoisomerase I inhibitor-containing ADC (eg, sacituzumab govitecan or fam-trastuzumab deruxtecan-nxki). Received prior systemic anticancer therapy including investigational agents within 4 weeks (or 5 half-lives, whichever is shorter) before the start of induction treatment. Received prior radiotherapy within 2 weeks of start of study intervention, or has radiation-related toxicities, requiring corticosteroids. Note: Two weeks or fewer of palliative radiotherapy for non-CNS disease is permitted. The last palliative radiotherapy treatment must have been performed at least 7 days before the first dose of study intervention. Received a live or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines is allowed. Refer to Section 6.5 for information on COVID-19 vaccines. Is currently receiving a strong inducer/inhibitor of CYP3A4 that cannot be discontinued for the duration of treatment with study intervention. The required washout period before starting sac-TMT is 2 weeks. Note: A list of strong inhibitors or inducers of CYP3A4 can be found at the following website: https://www.fda.gov/drugs/drug-interactions-labeling/drug-development-and-druginteractions-table-substrates-inhibitors-and-inducers Prior/Concurrent Clinical Study Experience Has received an investigational agent or has used an investigational device within 4 weeks prior to study intervention administration. Diagnostic Assessments Diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the f
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Testing: stratified log-rank test for comparison of the 2 arms. Estimation of hazard ratio and its 95% CI: Stratified Cox model with Efron’s tie handling method NAME OF THE RESULT: Progression-free survival (PFS) PERIOD OF TIME WHERE TE MEASUREMENT WILL BE CONDUCTED AND WHICH WILL ALLOW OBTAINING THE PRIMARY RESULT: From randomization to the first documented disease progression or death due to any cause, whichever occurs first;Testing: stratified log-rank test for comparison of the 2 arms. Estimation of hazard ratio and its 95% CI: Stratified Cox model with Efron’s tie handling method NAME OF THE RESULT: Overall Survival (OS) PERIOD OF TIME WHERE TE MEASUREMENT WILL BE CONDUCTED AND WHICH WILL ALLOW OBTAINING THE PRIMARY RESULT: From randomization to death due to any cause | — |
Secondary
| Measure | Time frame |
|---|---|
| Testing: stratified log-rank test for comparison of the 2 arms. Estimation of hazard ratio and its 95% CI: Stratified Cox model with Efron’s tie handling method NAME OF THE RESULT: Progression-free survival 2 (PFS2) as assessed by investigator PERIOD OF TIME WHERE TE MEASUREMENT WILL BE CONDUCTED AND WHICH WILL ALLOW OBTAINING THE PRIMARY RESULT: From randomization to the documented subsequent objective disease progression after initiation of new anticancer therapy or death due to any cause, whichever occurs first;Testing: stratified log-rank test for comparison of the 2 arms. Estimation of hazard ratio and its 95% CI: Stratified Cox model with Efron’s tie handling method NAME OF THE RESULT: Progression-free survival (PFS) PERIOD OF TIME WHERE TE MEASUREMENT WILL BE CONDUCTED AND WHICH WILL ALLOW OBTAINING THE PRIMARY RESULT: From randomization to the first documented disease progression or death due to any cause, whichever occurs first;Testing: stratified log-rank test for comparison of the 2 arms. Estimation of hazard ratio and its 95% CI: Stratified Cox model with Efron’s tie handling method NAME OF THE RESULT: Overall Survival (OS) PERIOD OF TIME WHERE TE MEASUREMENT WILL BE CONDUCTED AND WHICH WILL ALLOW OBTAINING THE PRIMARY RESULT: From randomization to death due to any cause | — |
Countries
Argentina, Australia, Austria, Belgium, Brazil, Canada, Chile, China, Colombia, Czech Republic, Denmark, Finland, France, Germany, Greece, Hungary, Ireland, Israel, Italy, Japan, Korea South, Mexico, Nederland, New Zealand, Norway, Peru, Poland, Puerto Rico, Singapore, Spain, Sweden, Taiwan, Thailand, Turkey, United Kindgdom, United States
Contacts
Public ContactNELVA GARCIA
MERCK SHARP & DOHME PERU S.R.L.
Outcome results
None listed