NCT06157541

T Cells and Pembrolizumab for Recurrent and Newly Diagnosed Glioblastoma

Phase I/II Clinical Trial of Allogeneic Cytomegalovirus-specific T Cells in Combination With Pembrolizumab for Recurrent and Newly Diagnosed Glioblastoma Multiforme

• Status: Recruiting
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 58 (estimated)
• Sponsor: Queensland Institute of Medical Research · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The goal of this clinical trial is to test a combined therapy approach (allogeneic cytomegalovirus \[CMV\]-specific T cells and pembrolizumab) in patients with brain cancer. The type of brain cancer being studied is glioblastoma multiforme/astrocytoma grade 4. The purpose of part 1 of this study is to determine the maximum-tolerated dose and/or recommended dose(s) for future exploration of allogeneic CMV-specific T cells as monotherapy or in combination with pembrolizumab in patients with recurrent GBM/astrocytoma grade 4. Part 2 of the study aims to investigate the anti-tumour activity of allogeneic CMV-specific T cells as monotherapy or in combination with pembrolizumab, assessed by magnetic resonance imaging and survival, in patients with recurrent or newly diagnosed GBM/grade 4 astrocytoma.

Detailed description

This is a multi-centre, non-randomised, open-label, dose escalation and expansion trial of allogeneic cytomegalovirus (CMV)-specific T cells as monotherapy and in combination with pembrolizumab in participants with recurrent and newly diagnosed glioblastoma multiforme (GBM)/astrocytoma grade 4. The trial will be conducted in two parts. Part 1 is a single-arm, sequential 3+3 dose-escalation of allogeneic CMV-specific T cells as a monotherapy and in combination with a fixed dose of pembrolizumab to determine the recommended dose(s) for future exploration. Up to 18 participants will be recruited for part 1. Part 2 will involve two arms and will examine the clinical impact of the CMV-specific T cells as monotherapy and in combination with pembrolizumab. Forty participants will be recruited for part 2 - 20 with newly diagnosed GBM/astrocytoma grade 4 and 20 with recurrent GBM/astrocytoma grade 4. Part 2 will only be initiated if the data and safety monitoring board (DSMB) determines that the proposed dose level(s) for future exploration are safe and well tolerated. Additional groups may be explored depending on emergent safety, pharmacodynamics and/or clinical efficacy data. Following screening and enrolment, each participant will receive four weekly infusions (Q1W) of allogeneic CMV-specific T cells, followed by up to 18 infusions of pembrolizumab. Pembrolizumab infusions will commence seven days (±3 days) after the final T-cell infusion, and be administered every 6 weeks (Q6W). The total duration of participation for each participant is approximately 26 months. Efficacy of the combination therapy will be evaluated according to the modified Response Assessment in Neuro-Oncology (RANO) and immunotherapy (i)RANO criteria, through radiographic imaging. For group A and group B the appropriate measures for progression-free survival (PFS), overall survival (OS), disease control rate and duration of response will be assessed.

Conditions

• Glioblastoma Multiforme
• Astrocytoma, Grade IV

Interventions

Type	Name	Description
BIOLOGICAL	Allogeneic cytomegalovirus-specific T cells	Allogeneic cytomegalovirus (CMV)-specific T cells generated from the blood of healthy CMV-seropositive donors
DRUG	Pembrolizumab	A humanised immunoglobulin G4 (IgG4) monoclonal antibody (mAb) specific for the programmed cell death 1 (PD-1) receptor

Timeline

• Start date: 2024-02-08
• Primary completion: 2026-04-01
• Completion: 2028-01-01
• First posted: 2023-12-06
• Last updated: 2024-05-31

Locations

4 sites across 1 country: Australia

Regulatory

• FDA-regulated drug study