Clinical Trial to investigate the feasibility, safety, and tolerability of BMS-986504 in patients with recurrent MTAP-deleted Glioblastoma

Exclusion Criteria32

• Multicentric / multifocal tumour in which safe maximal resection is not feasible
• Tumour involves cerebellum, brainstem, or deep basal ganglia
• Contraindication to surgery
• Prior neurosurgical biopsy or resection within 28 days prior to registration
• Patients who require urgent resection for mass effect, cerebral oedema, or hydrocephalus in the opinion of the treating neurosurgeon
• Evidence of acute intracranial/intra-tumoural haemorrhage, which requires urgent intervention
• History of CNS bleeding as defined by stroke or arterial thrombosis (e.g., stroke or transient ischaemic attack) within 6 months prior to registration
• Patients with contraindications to MRI or unwilling to undergo MRI
• Prior treatment with MATA2 inhibitor or a PRMT5 inhibitor
• Prior treatment with bevacizumab or immunotherapy. Note: Patients who have received lomustine are eligible
• Administration of any non-cytotoxic potential anti-tumour agent and or herbal preparation/medications within 7 days of planned biopsy
• Use of therapeutic anticoagulation. Note: Prophylactic low molecular weight heparins and low dose aspirin is allowed
• Treatment with immunosuppressive medications. Note: Low-dose corticosteroids (less than or equal to 2 mg/day dexamethasone or equivalent) for tumour-associated oedema is permitted. Patients who require corticosteroids > 2 mg/day dexamethasone (or equivalent) for acute emergencies during the screening window will be eligible if the corticosteroid dosing reduces to less than or equal to 2 mg/day dexamethasone (or equivalent) at least one day prior to the initial trial-mandated biopsy
• Ongoing need for a medication known as a strong inhibitor or strong inducer of CYP3A4 and/or P-glycoprotein (P-gp) or a proton-pump inhibitor that cannot be switched to alternative treatment prior to registration. The following drug interaction databases and other literature can be utilised to determine the CYP3A4/P-gp inhibitors and inducers: https://www.fda.gov/drugs/drug-interactions-labeling/drugdevelopment-and-druginteractions-table-substratesinhibitors-and-inducers; https://druginteractions.medicine.iu.edu/MainTable.aspxhttps://druginteractions.medicine.iu.edu/MainTable.aspx.
• Ongoing need for a medication with a known risk of Torsades de Pointes that cannot be switched to alternative treatment prior to registration
• Significant cardiac dysfunction defined as:
• Unstable angina pectoris or myocardial infarction within 6 months prior to registration
• Congestive heart failure greater than or equal to New York Heart Association Class 3 within 6 months prior to registration
• Left ventricular ejection fraction (LVEF) < 50%
• Prolonged QTc > 470 milliseconds or medical or immediate family history of congenital Long QT Syndrome
• Symptomatic or uncontrolled atrial fibrillation or other arrhythmia within 6 months prior to registration
• Gastrointestinal tract disease causing inability to take oral medication, malabsorption syndrome, gastric/jejunal tube feeds, uncontrolled inflammatory GI disease (e.g., Crohn’s disease, ulcerative colitis)
• Active tuberculosis
• Severe infection within 4 weeks prior to registration. A severe infection is defined as an infection that leads to septic shock, organ dysfunction, or admission to intensive care within four weeks of a patient's registration. It also includes any active, uncontrolled infection, such as fungemia or bacteraemia
• Treatment with a live, attenuated vaccine within 4 weeks prior to registration, or anticipation of need for such a vaccine during the study
• Patients are excluded if they have had another malignancy or received treatment for another malignancy within two years of enrolment. The only exceptions are patients with adequately treated cervical carcinoma in situ, basal cell carcinoma, or squamous cell carcinoma of the skin. Patients with a history of other malignancies are eligible if they have been treated with curative intent or continuously disease free for at least 2 years after definitive primary treatment
• Major surgical procedure, within 4 weeks prior to registration
• History of idiopathic pulmonary fibrosis, organising pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis
• Patient is pregnant or breast-feeding
• Known severe hypersensitivity to study treatment and/or any of its excipients
• Prior allogeneic stem cell or solid organ transplantation
• Presence of any psychological, social, geographical, or other condition for which, in the opinion of the site Investigator, participation would not be in the best interest of the patient (e.g., compromise the well-being) or that could prevent, limit, or confound the protocol-specified assessments