NCT06180733

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

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

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 12 (estimated)
• Sponsor: University Medical Center Groningen · Academic / Other
• Sex: Female
• Age: 18 Years
• Healthy volunteers: Not accepted

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.

Detailed description

Objective: Based on the success of the pilot feasibility study, we propose a phase 2 trial 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). Study design: Patients will be treated with neo-adjuvant pembrolizumab (200mg IV Q3W, for a total of 9 administrations), followed by SoC surgery and adjuvant therapy where indicated. Tumor responses to pembrolizumab will be assessed by a pathologist (primary endpoint) using material from the SoC surgery. In addition, tumor response will be evaluated by MRI (secondary endpoint) after the second, fourth, sixth, and last cycle of pembrolizumab. In case of suspicion of progressive disease, the hysterectomy will immediately take place. Peripheral blood and tumor samples will be used to explore dynamics of tumor and immune responses during therapy. Follow-up: Adverse events will be followed up to 6 months after the final pembrolizumab administration. Outside the study protocol patients will be followed-up according SoC guidelines for uterine cancer. Patients will be asked to participate in follow-up of disease progression (2-year recurrence-free survival). Study population: Primary MMRd UC patients at high-risk of recurrence (endometrioid grade 3 or clear cell histology) who are intended to be treated with a hysterectomy. Intervention: Pembrolizumab, 200mg IV Q3W for a total of 9 administrations per patient, prior to SoC therapy.

Conditions

• Endometrial Cancer

Interventions

Type	Name	Description
DRUG	Pembrolizumab Injection [Keytruda]	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.

Timeline

• Start date: 2023-12-01
• Primary completion: 2027-12-30
• Completion: 2028-01-01
• First posted: 2023-12-22
• Last updated: 2023-12-22

Locations

1 site across 1 country: Netherlands

Regulatory

• FDA-regulated drug study