Phase I/II clinical trial evaluating the safety and efficacy of allogeneic cytomegalovirus-specific T cells in combination with pembrolizumab for recurrent and newly diagnosed glioblastoma multiforme

ACTRN 12623001126606

Brief Summary

This study aims to assess the safety and potential effectiveness of a new treatment combining two different cancera disease where abnormal cells split without control and spread to other nearby body tissue and/or organs treatments, a T cell-based immunotherapya treatment that uses a person's immune system to fight cancer and pembrolizumab (a drug that is used to prevent cancer cellsthe basic structural and functional unit of all living things from hiding from T cells), for glioblastoma multiforme (GBM) or astrocytoma gradea description of how abnormal cancer cells and tissue look under a microscope when compared to healthy cells 4.

Intervention/Treatment

• Other: Allogeneic cytomegalovirus (CMV)-specific T cells.
• Drug: Pembrolizumab.

Inclusion Criteria

1. Participants who are at least 18 years of age on the day of signing informed consenta process in which a patient receives detailed information about a procedure or treatment, including its potential risks, benefits, and alternatives. The patient then has the opportunity to understand the information and voluntarily agree to the procedure or treatment. with histologically confirmed diagnosisthe process of identifying a disease based on signs and symptoms, patient history and medical test results of GBM or astrocytoma Grade 4.
   • For participants with recurrent GBM or astrocytoma grade 4, histological confirmation of primary diagnosis is available:
     • First occurrence of disease progression with radiological confirmation greater than or equal to 12 weeks from completion of radiation therapya treatment that uses controlled doses of radiation to damage or kill cancer cells.
     • Where surgical resectionsurgical removal of tissue or part/all of an organ of recurrent disease occurred, histological confirmation of GBM or
       astrocytoma Grade 4 is required.
   • For participants with newly diagnosed GBM or astrocytoma Grade 4, histological confirmation of diagnosis is required:
     • 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: Participant eligibility will not be dependent on IDH status. Histological confirmation using the 2016 or 2021 WHO Classification of Tumours of the CNS is acceptable and
     classification edition will be noted.
2. Male participants: A male participant must agree to use a contraception as detailed in the protocol during the treatment period and for at least 180 days after the last dosethe amount of medication taken of study treatment and refrain from donating sperm during this period.
3. Female participants: A female participant is eligible to participate if she is not pregnant, not undergoing in vitro fertilisation and not breastfeeding, and at least one of the following conditions applies:
   • Not a woman of childbearing potential (WOCBP)
     OR
   • A WOCBP who agrees to follow the contraceptive guidance during the treatment period and for at 120 days after the last dose of study treatment.
4. The participant (or legally acceptable representative if applicable) provides 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.
5. Participants who have AEs due to previous anti-cancer therapies must have recovered to less than or equal to Grade 1 or baseline. Participants with endocrine-related AEs who are adequately treated with hormonea chemical substance produced by glands in the endocrine system that regulates various functions in the body replacement or participants who have less than or equal to Grade 2 neuropathy are eligible. Participants with greater than Grade 1 AE(s) 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 riskthe possibility that something bad will happen of study-related AEs or interfere with the integrity of the study outcome.
6. For participants with disease progression, this should be the first evidence of measurable disease based on modified RANO criteria. Lesions situation in a previously irradicated area are considered measurable if progression has been demonstrated in such lesions.
7. CMV-positive serology.
8. Provision of consent for the use of archival formalin-fixed, paraffin embedded (FFPE) or fresh tumoura tissue mass that forms from groups of unhealthy cells tissuea group of cells that work together to perform a function obtained at the time of surgical resection or excisional biopsyremoval of a section of tissue to analyse for cancer cells.
   Note: Clinical outcome predictors IDH1/2, MGMT status, ATRX, EGFR amplification and Ki-67 not available at screeningtesting for cancer or conditions that can lead to cancer before symptoms appear, also known as cancer screening will be analysed following the completion of recruitment.
9. Have an Eastern Cooperative Oncologythe study, diagnosis and treatment of cancer Group (ECOG) performance status of 0 or 1. Evaluation of ECOG is to be performed within 7 days prior to the first dose of study intervention.
10. Have a life expectancy of at least 6 months.
11. Have adequate organ function as defined in the protocol. Specimens must be collected within 10 days prior to the start of study intervention.
12. Have availability of an HLA-matched batch of allogeneic CMV-specific T cells.
13. Provision of consent to access to Medicare Benefits Schedule (MBS) and Pharmaceutical Benefits Scheme (PBS) patient/provider health information collected by Services Australia (phase II participants only).
14. Criteria for known Hepatitis B and C positive participants:
    • Hepatitis B and C screening tests are not required unless:
      1. Known history of HBV or HCV infectiona condition where harmful pathogens, such as bacteria, viruses or parasites, have entered the body.
      2. As mandated by local health authority.
    • Hepatitis B-positive participants:
      1. Participants who are HBsAg positive are eligible if they have received HBV anti-viral therapy for at least 4 weeks and have undetectable HBV viral load prior to enrolment.
      2. Participants should remain on anti-viral therapy throughout study intervention and follow local guidelines for HBV anti-viral therapy post completion of study intervention.
    • Participants with history of HCV infection are eligible if HCV viral load is undetectable at
      screening.