ATM-Inhibitor WSD0628 in Combination With Radiation Therapy for Treatment of Recurrent High-Grade Glioma

Inclusion Criteria: * Age ≥ 18 years * Histological confirmation of one of the following: * Glioblastoma, IDH-wildtype * Grade 3 or 4 IDH1/2 mutant astrocytoma (2021 WHO classification) * Measurable disease as defined in Section 11.0 * Disease progression after previous treatment for glioma with radiation and chemotherapy * Minimum life expectancy of at least 3 months * Group C only: Dose Expansion, Brain Tumor Penetration Group: plan for radiosurgery and surgical resection as part of routine clinical care * ECOG Performance Status (PS) 0, 1 or 2 (Appendix I) * The following laboratory values obtained ≤15 days prior to registration: * Hemoglobin ≥9.0 g/dL * Leukocytes ≥3.0 x 109/L * Absolute neutrophil count (ANC) ≥1500/mm3 or 1.5 x 109/L * Platelet count ≥100,000/mm3 or 100 x 109/L * Total bilirubin ≤1.5 x ULN and \<3 mg/dL for patients with Gilbert's disease * Alanine aminotransferase (ALT) and aspartate transaminase (AST) ≤3 x ULN * PT/INR/aPTT ≤1.5 x ULN OR if patient is receiving anticoagulant therapy and INR or aPTT is within target range of therapy * Calculated creatinine clearance ≥45 ml/min using the Cockcroft-Gault formula below: * Creatinine clearance for males = (140-age)(weight in kg)(72)(serum creatinine inmgdL⁄) * Creatinine clearance for females = (140-age)(weight in kg)(0.85)(72)(serum creatinine inmgdL⁄) * Negative pregnancy test done ≤7 days prior to registration, for persons of childbearing potential only * Willing to take light-protective measures during the study and for two weeks after their last dose of WSD0628 * Provide written informed consent * Willing to return to enrolling institution for follow-up (during the Active Monitoring Phase of the study) * Willingness to provide mandatory tissue specimens for correlative research Exclusion Criteria: * Any of the following because this study involves an investigational agent, the genotoxic, mutagenic, and teratogenic effects of which on the developing fetus and newborn are unknown: * Pregnant persons * Nursing persons * Persons of childbearing potential and persons able to father a child who are unwilling to employ adequate contraception * Uncontrolled intercurrent illness including, but not limited to: * ongoing or active infection * symptomatic congestive heart failure * unstable angina pectoris * cardiac arrhythmia * or psychiatric illness/social situations that would limit compliance with study requirements * Any of the following cardiac criteria: * Marked baseline prolongation of QT/QTc interval (e.g., repeated demonstration of a QTc interval \>480 milliseconds (ms) (CTCAE Grade 1) using Fredericia's QT correction formula. * History of additional risk factors for Torsades de Pointes (e.g., heart failure, hypokalemia, family history of Long QT. Syndrome). * Use of concomitant medications that prolong the QT/QTc interval * History of myocardial infarction ≤6 months prior to registration, or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias * Known coagulopathy increasing the risk of bleeding or history of clinically significant hemorrhage, including significant intracranial tumor related hemorrhage * Any of the following medications: * Enzyme-inducing anticonvulsants within two weeks of enrollment NOTE: Patients can be enrolled after a change to non-enzyme inducing anticonvulsants) * Patients taking more than 8 mg of dexamethasone per day (or equivalent steroid dose) at time of enrollment * Any of the following prior therapies: * Radiation therapy \<= 26 weeks prior to registration (including gamma tiles) * Chemotherapy, immunotherapy, or any investigational drug \<= four weeks prior to registration, * or carmustine (BCNU) or lomustine (CCNU) \<= six weeks prior to registration * Past medical history of interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonitis which required steroid treatment, or any evidence of clinically active interstitial lung disease * History of hypersensitivity to active or inactive excipients of WSD0628 or drugs with a similar chemical structure or class to WSD0628 * Refractory nausea and vomiting if not controlled by supportive therapy, chronic gastrointestinal diseases, inability to swallow the formulated product or previous significant bowel resection that would preclude adequate absorption of WSD0628 * Uncontrolled hypertension * History of severe brain-injury or stroke * Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm