COMBinATion nivolumab and decitabine for treatment of primary GlioBlastoma (COMBAT-GB)
Newly-diagnosed primary glioblastoma
COMBAT- GB is a phase 1, non-randomised, dose escalation trial. It is looking for an effect of the “enhancer” drug ASTX727, given before immunotherapy (nivolumab), on patient outcomes and tumour responses to the immunotherapy. The trial aims to establish safety and efficacy of this novel drug combination and establish the best possible dose. Nivolumab has been given to patients in the past with glioblastoma, and ASTX727 has been given to patients with leukaemia. Each participant will receive 1 dose of ASTX727 for 5 consecutive days. The doses will vary as the safety profile of the drug is established throughout the trial. The initial dose will be the lowest dose, and the first patient must complete the safety window prior to further recruitment. All participants will receive a single IV dose of Nivolumab immunotherapy on Day 8. After receiving the trial medication, all participants receive normal standard of care treatment: surgical resection of their tumour, followed by post-operative radio/chemotherapy regimen, as determined by their normal clinical care team. All participants will be actively followed up for 4 months. Beyond this, disease progression and survival data will be collected by the research team at sites from the participant’s medical notes at 6 months and then 6-monthly until 6 months after the last participant is recruited. All participants will undergo a brain MRI scan before and after their surgical tumour resection, as per normal standard of care treatment. In addition, participants will also be offered an optional research tumour biopsy at baseline, before they take the trial medications. Participants who consent to this will have a brain CT scan after the biopsy, in addition to their standard of care MRI scans.
Current inclusion criteria as of 05/03/2026: 1. Aged 18 years and over on day of signed informed consent 2. Ability to provide written informed consent. 3. Willing and able to comply with the protocol scheduled follow-up visits and examinations for the duration of the trial. 4. WHO Performance status 0-1 5. Newly suspected glioblastoma on Gadolinium-enhanced MRI scan and reviewed in the local Neuro-oncology multidisciplinary meeting, which is amenable for maximal resection. 6. Patients with tumours that do not exert significant mass effect and/or have significant oedema and where a delay to surgery is thought will lead to undue harm as determined by the MDT. 7. Male and female participants of reproductive potential must agree to avoid becoming pregnant or impregnating a partner and adhere to highly effective contraception requirements whilst receiving decitabine/nivolumab and for 6 months after their last dose of decitabine for female participants and for 3 months after their last dose of decitabine for male participants. ----- Previous inclusion criteria as of 07/03/2024: 1. Aged 18 years and over on day of signed informed consent 2. Ability to provide written informed consent. 3. Willing and able to comply with the protocol scheduled follow-up visits and examinations for the duration of the trial. 4. WHO Performance status 0-1 5. Newly suspected glioblastoma on Gadolinium-enhanced MRI scan and reviewed in the local Neuro-oncology multidisciplinary meeting, which is amenable for maximal resection. 6. Patients with tumours that do not exert significant mass effect and/or have significant oedema and where a delay to surgery is thought will lead to undue harm as determined by the MDT. 7. Male and female participants of reproductive potential must agree to avoid becoming pregnant or impregnating a partner and adhere to highly effective contraception requirements whilst receiving ASTX727/Nivolumab and for 6 months after their last dose of ASTX727 for female partici
Current exclusion criteria as of 05/03/2026: 1. Patients with suspected glioblastoma who have significant mass effect and need emergency surgery. 2. Any concern on initial MRI that the tumour may not be a primary glioblastoma. 3. Patients that have previously received immunotherapy or hypomethylating agents. 4. Impaired gastrointestinal function that may significantly alter absorption of decitabine. 5. Has a known diagnosis of immunodeficiency (human immunodeficiency virus [HIV] 1/2 antibodies) or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment excluding steroids. 6. Another advanced malignancy or history of another early malignancy that the investigator considers is likely to impact life expectancy. 7. Has an active autoimmune disease requiring systemic treatment within the past 3 months or a documented history of clinically severe autoimmune disease. Patients with vitiligo, resolved childhood asthma/atopy/psoriasis or hypothyroidism stable on hormone replacement would be an exception. Patients that require intermittent use of bronchodilators or local steroid injections are not excluded. 8. Has evidence of or a history of interstitial lung disease or (non-infectious) pneumonitis. 9. History of severe allergic reactions to any unknown allergens or any components of the trial drugs. 10. Is pregnant or breastfeeding or expecting to conceive children within the projected duration of the trial, starting with the screening visit through 6 months after the last dose of trial treatment for female participants, or is expecting to father children in that time through 3 months after the last dose of trial treatment for male participants. 11. Has known active hepatitis B or hepatitis C. 12. Concurrent or recent (<28 days) treatment in any other interventional clinical trial involving novel surgical technique or medication. 13. Any psychological, social or medical condition, physical examination finding or laboratory abnormal