endometrial cancer Uterine cancer
Conditions
Interventions
Pembrolizumab, 200mg IV Q3W for a total of 9 administrations per patient, prior
to SoC therapy.
Sponsors
Universitair Medisch Centrum Groningen
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: - 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. - 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. - The participant (or legally acceptable representative if applicable) provides written informed consent for the trial.
Exclusion criteria
Exclusion criteria: - A WOCBP who has a positive serum pregnancy test at screening. - 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). - 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. - Has received prior radiotherapy within 2 weeks of start of study treatment or radition-related toxicities requiring corticosteroids. Note: Two weeks or fewer of palliative radiotherapy for non-CNS disease with a 1-week washout is permitted. - 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. - Has received an investigational agent or has used an investigational device within 4 weeks prior to study intervention administration. - 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. - 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. - 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. - Has severe hypersensitivity (>=Grade 3) to pembrolizumab and/or any of its excipients. - Has active autoimmune disease that has required systemic treatment in the past 2 years except replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid). - Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis. - Has an active infection requiring systemic therapy. - Has a known history of Human Immunodeficiency Virus (HIV). Note: No HIV testing is required unless mandated by local health authority. - 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. Note: no testing for Hepatitis B and Hepatitis C is required unless mandated by local health authority. - Has not adequately recovered from major surgery or has ongoing surgical complications. - 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 treatin
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The primary endpoint is the fraction of patients that achieve a major pathologic response (MPR) after 9 cycles of pembrolizumab. MPR was chosen in line with neo-adjuvant vs adjuvant ICB trials in other cancer types (e.g. the NADINA trial; NCT04949113 for melanoma patients) and will be used to inform the design of a randomized follow-up trial. The trial is considered positive if a >=74% MPR rate is observed (see also sample size calculation). | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary endpoints are the radiologic response rates, recurrence-free survival (RFS) at 2 years from disease diagnosis, and the safety and tolerability of 9 cycles of pembrolizumab. Exploratory endpoints relate to the nature of the immune responses in peripheral blood and tumor, the involvement of Tumor Draining Lymph Nodes (TDLN), and changes in circulating tumor DNA (ctDNA) during treatment. | — |
Countries
Netherlands
Outcome results
None listed