Pembrolizumab for Mismatch repair deficient endometrial cancer|Uterine cancer

Inclusion criteria

• {"criterion_text":"- Female participants who are at least 18 years of age on the day of signing informed consent with histologically confirmed primary diagnosis of G3/CC MMRd uterine cancer who are intended to be treated with hysterectomy."}
• {"criterion_text":"- A female participant is eligible to participate if she is not pregnant, not breastfeeding, is not a woman of childbearing potential (WOCBP) or agrees to follow contraceptive guidance during the treatment period and at least until standard-of-care hysterectomy."}
• {"criterion_text":"- The participant (or legally acceptable representative if applicable) provides written informed consent for the trial."}

Exclusion criteria

• {"criterion_text":"- A WOCBP who has a positive serum pregnancy test at screening."}
• {"criterion_text":"- Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients."}
• {"criterion_text":"- Has active autoimmune disease that has required systemic treatment in the past 2 years except replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid)."}
• {"criterion_text":"- Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis."}
• {"criterion_text":"- Has an active infection requiring systemic therapy."}
• {"criterion_text":"- Has a known history of Human Immunodeficiency Virus (HIV)."}
• {"criterion_text":"- Has a known history of Hepatitis B (defined as Hepatitis B surface antigen [HBsAg] reactive) or known active Hepatitis C virus (defined as HCV RNA [qualitative] is detected) infection."}
• {"criterion_text":"- Has not adequately recovered from major surgery or has ongoing surgical complications."}
• {"criterion_text":"- Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject’s participation for the full duration of the study, or is not in the best interest of the subject to participate, in the opinion of the treating investigator."}
• {"criterion_text":"- Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial."}
• {"criterion_text":"- Is pregnant or breastfeeding, or expecting to conceive within the projected duration of the study, starting with the screening visit through 120 days after the last dose of trial treatment."}
• {"criterion_text":"- Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX-40, CD137)."}
• {"criterion_text":"- Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks [could consider shorter interval for kinase inhibitors or other short half-life drugs] prior to allocation."}
• {"criterion_text":"- Has received prior radiotherapy within 2 weeks of start of study treatment or radiation-related toxicities requiring corticosteroids. Note: Two weeks or fewer of palliative radiotherapy for non-CNS disease with a 1-week washout is permitted."}
• {"criterion_text":"- Has received a live vaccine or live-attenuated vaccine within 30 days before to the first dose of study intervention. Administration of killed vaccines and Covid vaccines is allowed."}
• {"criterion_text":"- Has received an investigational agent or has used an investigational device within 4 weeks prior to study intervention administration."}
• {"criterion_text":"- Has a 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 first dose of study drug."}
• {"criterion_text":"- Has a known additional malignancy that is progressing or has required active treatment within the past 3 years. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g. breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded."}
• {"criterion_text":"- Has known active CNS metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, i.e. without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study treatment."}

Primary endpoints

• {"endpoint_text":"- The main study endpoint is the fraction of patients that achieve a MPR. that the study is considered positive if neo-adjuvant pembrolizumab induces MPRs in at least 74% of patients.","definition_or_measurement_approach":"Major pathologic response (MPR) assessed after 9 cycles of pembrolizumab; study considered positive if MPR observed in ≥74% of patients."}

Secondary endpoints

• {"endpoint_text":"- The objective response rate of the tumor determined by radiologic assessment using MRI and RECIST1.1.","definition_or_measurement_approach":"Objective response assessed by radiologic MRI using RECIST 1.1 criteria."}
• {"endpoint_text":"- Recurrence-free survival 2 years from disease diagnosis.","definition_or_measurement_approach":"Recurrence-free survival defined as number of patients alive without any progression or recurrence at two years from disease diagnosis."}
• {"endpoint_text":"- The safety and tolerability of 9 cycles of neo-adjuvant pembrolizumab in the treatment of MMRd UC.","definition_or_measurement_approach":"Safety and tolerability assessed during and after administration of 9 cycles of neo-adjuvant pembrolizumab (adverse events, tolerability measures)."}

Netherlands

Earliest CTIS Part Ii Submission Date

03-09-2024

Latest Decision Or Authorization Date

17-11-2025

Processing Time Days

440

Number Of Sites

2

Number Of Participants

12

Primary sponsor

Full Name

Universitair Medisch Centrum Groningen

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Netherlands

Third parties

• {"country":"","full_name":"MSD","duties_or_roles":"Monetary support","organisation_type":""}
• {"country":"","full_name":"KWF","duties_or_roles":"Monetary support","organisation_type":""}