T Cells and Pembrolizumab for Recurrent and Newly Diagnosed Glioblastoma

NCT06157541 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: P3894 / MSD-MK3475-E78
• Study Type: interventional
• Target: 58
• Locations: 1 country
• Sites: 4

Brief 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.

Conditions

Glioblastoma Multiforme; Astrocytoma, Grade IV

Keywords

immunotherapy; T cells; pembrolizumab; glioblastoma

Outcome Measures

Primary Outcomes (7)

• Incidence of dose-limiting toxicities

  Part 1 - Primary Endpoint 1

  Within 49 days of receiving the first dose of study drug

• Incidence of adverse events and clinically significant changes in laboratory parameters, vital signs, and electrocardiograms (ECGs)

  Part 1 - Primary Endpoint 2

  Within 49 days of the first dose of study drug

• Percentage of participants with confirmed complete response (CR) or partial response (PR)

  Part 2 - Primary Endpoint 1

  Within 25 months of the first dose of study drug

• Percentage of participants with confirmed complete response (CR), partial response (PR), or stable disease (SD)

  Part 2 - Primary Endpoint 2

  Within 25 months of the first dose of study drug

• Duration of response

  Part 2 - Primary Endpoint 3

  Within 25 months of the first dose of study drug

• Overall survival (percentage of participants alive)

  Part 2 - Primary Endpoint 4

  6 months

• Progression-free survival (percentage of participants with no evidence of further disease progression)

  Part 2 - Primary Endpoint 5

  6 months

Secondary Outcomes (6)

• Percentage of participants with confirmed CR or PR

  Within 25 months of the first dose of study drug

• Percentage of participants with confirmed CR, PR, or SD

  Within 25 months of the first dose of study drug

• Duration of response

  Within 25 months of the first dose of study drug

• Overall survival (percentage of participants alive)

  6 months

• Progression-free survival (percentage of participants with no evidence of further disease progression)

  6 months

Study Arms (3)

Part 1

EXPERIMENTAL

Patients with recurrent disease. Interventions: * allogeneic CMV-specific T cells (cell suspension for infusion), dose cohorts: 2 × 10\^7 cells, 4 × 10\^7 cells, 8 × 10\^7 cells; 4 infusions; administered weekly * pembrolizumab 400 mg (solution for injection); 18 infusions; administered every 6 weeks

Biological: Allogeneic cytomegalovirus-specific T cells; Drug: Pembrolizumab

Part 2 Group A

EXPERIMENTAL

Patients with recurrent disease. Interventions: * allogeneic CMV-specific T cells (cell suspension for infusion), maximum-tolerated dose identified in phase I; 4 infusions; administered weekly * pembrolizumab 400 mg (solution for injection); 18 infusions; administered every 6 weeks

Biological: Allogeneic cytomegalovirus-specific T cells; Drug: Pembrolizumab

Part 2 Group B

EXPERIMENTAL

Patients with newly diagnosed disease. Interventions: * allogeneic CMV-specific T cells (cell suspension for infusion), maximum-tolerated dose identified in phase I; 4 infusions; administered weekly * pembrolizumab 400 mg (solution for injection); 18 infusions; administered every 6 weeks

Biological: Allogeneic cytomegalovirus-specific T cells; Drug: Pembrolizumab

Interventions

Allogeneic cytomegalovirus-specific T cells BIOLOGICAL

Allogeneic cytomegalovirus (CMV)-specific T cells generated from the blood of healthy CMV-seropositive donors

Also known as: CYT-101

Part 1; Part 2 Group A; Part 2 Group B

Pembrolizumab DRUG

A humanised immunoglobulin G4 (IgG4) monoclonal antibody (mAb) specific for the programmed cell death 1 (PD-1) receptor

Also known as: Keytruda

Part 1; Part 2 Group A; Part 2 Group B

Eligibility Criteria

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

You may qualify if:

• At least 18 years of age on the day of signing informed consent, with histologically confirmed diagnosis of GBM or astrocytoma Grade 4\^.
• a. For participants with recurrent GBM or astrocytoma grade 4, histological confirmation of primary diagnosis is available i. First occurrence of disease progression with radiological confirmation ≥12 weeks from completion of radiation therapy.
• ii. Where surgical resection of recurrent disease occurred, histological confirmation of GBM or astrocytoma Grade 4 is required.
• b. For participants with newly diagnosed GBM or astrocytoma Grade 4, histological confirmation of diagnosis is required i. Participant, in consultation with their treating clinicians, is willing to delay the commencement of standard of care adjuvant temozolomide until the completion of CMV-specific T cell therapy infusions.
• \^Note: Histological confirmation using the 2016 or 2021 World Health Organization (WHO) Classification of Tumours of the central nervous system (CNS) is acceptable and classification edition will be noted.
• Male participants: Must agree to use contraception during the treatment period and for at least 180 days after the last dose of study treatment and refrain from donating sperm during this period.
• Female participants: Must not be pregnant or undergoing in vitro fertilisation or breastfeeding, and at least one of the following conditions applies:
• Not a woman of childbearing potential (WOCBP) OR
• A WOCBP who agrees to follow contraceptive guidance during the treatment period and for at 120 days after the last dose of study treatment.
• Provision of written informed consent for the trial. Approved interpreters will be used for patients who do not have sufficient understanding of English for informed consent to be obtained without an interpreter.
• Participants who have AEs due to previous anti-cancer therapies must have recovered to ≤Grade 1 or baseline. Participants with endocrine-related AEs who are adequately treated with hormone replacement or participants who have ≤Grade 2 neuropathy are eligible. Participants with \>Grade 1 adverse events (AEs) due to previous anti-cancer therapies may be allowed to enrol on a case-by-case basis in discussion with the study Sponsor, if it is determined that it will not put the participant at a higher risk of study-related AEs or interfere with the integrity of the study outcome.
• For participants with disease progression, this should be the first evidence of measureable disease based on modified RANO criteria. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
• CMV-positive serology
• Provision of consent for the use of archival formalin-fixed, paraffin embedded or fresh tumour tissue obtained at the time of surgical resection or excisional biopsy.
• Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. Evaluation of ECOG is to be performed within 7 days prior to the first dose of study intervention.

You may not qualify if:

• A WOCBP who has a positive urine pregnancy test within 72 hours prior to the first dose of study intervention (see Appendix 3). If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
• 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.
• Has received prior systemic anti-cancer therapy or investigational agents within 4 weeks prior to study intervention, with the exception of temozolomide, which is permitted during the trial.
• Recurrent disease cohorts only: Has not yet recovered from all radiation-related toxicities not requiring corticosteroids other than dexamethasone, or has had radiation pneumonitis.
• Note: A 1-week washout is permitted for palliative radiation of non-CNS disease (≤2 weeks of radiotherapy). Participants receiving dexamethasone must be clinically stable and receiving a stable or weaning dose of ≤2 mg/day 1-2 weeks prior to the commencement of pembrolizumab.
• Has received a live vaccine or live-attenuated vaccine within 30 days prior to the first dose of study intervention. Administration of killed vaccines is allowed.
• Has received in an investigational agent, or has used an investigational device within 4 weeks prior to the first dose of study intervention.
• 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.
• Known additional malignancy that is progressing or has required active treatment within the past 5 years.
• Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, prostate cancer treated with radical prostatectomy, or carcinoma in situ, excluding carcinoma in situ of the bladder, who have undergone potentially curative therapy are not excluded. Participants with additional malignancy within the past 5 years may be allowed to enrol on a case-by-case basis, in discussion with the study Sponsor, if the malignancy is deemed of very low recurrence potential and the participant has completed curative intent therapy.
• Has a previous known GBM/astrocytoma grade 4 recurrence previously treated with surgery, radiotherapy and/or chemotherapy, and evidence of further progression or recurrence.
• 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 (e.g., thyroxine, insulin, or physiologic corticosteroid).
• Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
• Has an active infection requiring systemic therapy.

Sponsors & Collaborators

• Queensland Institute of Medical Research: lead
• CUREator: collaborator
• Merck Sharp & Dohme LLC: collaborator
• The Newro Foundation: collaborator
• Royal Brisbane and Women's Hospital: collaborator
• Princess Alexandra Hospital, Brisbane, Australia: collaborator
• Austin Hospital, Melbourne Australia: collaborator

Study Sites (4)

Newro Foundation

Bowen Hills, Queensland, 4006, Australia

RECRUITING

Royal Brisbane and Women's Hospital

Herston, Queensland, 4006, Australia

NOT YET RECRUITING

Princess Alexandra Hospital

Woolloongabba, Queensland, 4102, Australia

NOT YET RECRUITING

Austin Hospital

Heidelberg, Victoria, 3084, Australia

NOT YET RECRUITING

MeSH Terms

Conditions

Glioblastoma

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Study Officials

• Rajiv Khanna, PhD

  QIMR Berghofer Medical Research Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Michelle Neller, PhD

CONTACT

+61 7 3362 0412; immunotherapy@qimrberghofer.edu.au

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Phase I of the trial is a 3+3 dose escalation study involving 9-18 participants. Phase II will recruit two cohorts of 20 participants.

Study Record Dates

• First Submitted: November 26, 2023
• First Posted: December 6, 2023
• Study Start: February 8, 2024
• Primary Completion: April 1, 2026
• Study Completion (Estimated): January 1, 2028
• Last Updated: May 31, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

AU (4)