Neo-adjuvant Pembrolizumab as an Alternative Treatment for MMRd Uterine Cancer

NCT06180733 | Active Not Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: PAM-UMCG-0022022-003922-27
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to establish the fraction of patients that achieve a major pathological response (MPR) after 9 cycles of pembrolizumab, with the ultimate aim of informing a follow-up randomized trial. Participants will receive 9 cycles of pembrolizumab before their standard of care hysterectomy.

Conditions

Endometrial Cancer

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Establish fraction of patients that achieve major pathologic response

  The primary objective of this phase 2 trial is to establish the fraction of patients that achieve a major pathologic response (MPR) after 9 cycles of pembrolizumab, with the ultimate aim of informing a follow-up randomized trial. MPR was chosen as primary endpoint to align with ongoing randomized phase 3 ICB trials on neo-adjuvant vs. adjuvant treatment in other tumor types (e.g. the NADINA trial in melanoma; NCT04949113).

  Tumor tissue is collected during standard of care hysterectomy (6 months after baseline)

Secondary Outcomes (3)

• Radiologic response

  MRI is scheduled before start study drug (week 4), during treatment (week 11, 17, and 23) and before surgery (week 32)

• Recurrence Free Survival

  RFS will be assessed 2 years after baseline

• Safety and tolerability (Adverse Events)

  Through study completion, an average of 6 months per patient

Other Outcomes (4)

• The nature of the immune responses during treatment.

  Will be determined after study completion, an average of 1 year

• The involvement of TDLN in the immune responses on-treatment

  Will be determined after study completion, an average of 1 year

• Changes in circulating tumour DNA (ctDNA) during treatment

  Will be determined after study completion, an average of 1 year

Study Arms (1)

Primary MMRd endometrial cancer patients

EXPERIMENTAL

Drug: Pembrolizumab Injection [Keytruda]

Interventions

Pembrolizumab Injection [Keytruda] DRUG

Pembrolizumab (Keytruda), 200mg IV Q3W for a total of 9 administrations per patient, prior to standard-of-care surgery. Patients will be monitored for response and possible progression using MRI and pipelle biopsies.

Primary MMRd endometrial cancer patients

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University Medical Center Groningen: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

University Medical Centre Groningen

Groningen, Provincie Groningen, 9700 RB, Netherlands

Location

MeSH Terms

Conditions

Endometrial Neoplasms; Uterine Neoplasms; Lymphoma, Follicular

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Hans W Nijman, Prof. dr.

  University Medical Center Groningen, UMCG

  PRINCIPAL INVESTIGATOR

• Mathilde Jalving, Dr.

  University Medical Center Groningen, UMCG

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Head of Obstetrics and Gynecology, Prinicpal Investigator

Study Record Dates

• First Submitted: December 4, 2023
• First Posted: December 22, 2023
• Study Start: December 1, 2023
• Primary Completion (Estimated): December 30, 2027
• Study Completion (Estimated): January 1, 2028
• Last Updated: May 1, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1)