Using pembrolizumab before surgery for MMRd uterine cancer

Neo-adjuvant Pembrolizumab as an Alternative Treatment for MMRd Uterine Cancer, a Phase II Efficacy Study

This study is testing if giving pembrolizumab before surgery can help people with MMRd uterine cancer by seeing how well it shrinks their tumors.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 12 (estimated)
• Ages: 18 Years and up
• Sex: Female
• Sponsor: University Medical Center Groningen (Academic / other)
• Drugs / interventions: pembrolizumab, radiation, prednisone
• Locations: 1 site (Groningen)
• Trial ID: NCT06180733 on ClinicalTrials.gov

What this trial studies

This clinical trial aims to evaluate the effectiveness of neo-adjuvant pembrolizumab in patients with MMRd uterine cancer by assessing the rate of major pathological response (MPR) after 9 cycles of treatment. Participants will receive pembrolizumab injections every three weeks, followed by standard surgical treatment. Tumor responses will be evaluated through pathological assessment and MRI scans at various points during the treatment. The study also aims to explore the dynamics of tumor and immune responses through blood and tumor samples.

Who should consider this trial

Good fit: Ideal candidates are females aged 18 and older with histologically confirmed Grade 3 or clear cell MMRd uterine cancer who are scheduled for hysterectomy.

Not a fit: Patients who have previously received anti-PD-1, anti-PD-L1, or similar therapies may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could improve treatment outcomes for patients with MMRd uterine cancer by enhancing the effectiveness of subsequent surgical interventions.

How similar studies have performed: Other studies have shown promising results with neo-adjuvant immunotherapy approaches in various cancers, suggesting potential for success in this novel application.

Eligibility 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:

* 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 radiation-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 treating investigator.
* Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
* 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.

Where this trial is running

Groningen

• University Medical Centre Groningen — Groningen, Netherlands (Recruiting)

Study contacts

• Principal investigator: Hans W Nijman, Prof. dr. — University Medical Center Groningen, UMCG
• Study coordinator: Koen Brummel, Drs.

Conditions Endometrial Cancer; Uterine Cancer; MMRd; Grade 3; Clear Cell; Neo-adjuvant; Pembrolizumab