Tuvusertib in Astrocytoma With ATRX Mutation

Inclusion Criteria: 1. Written informed consent approved by the Independent Ethics Committee (IEC), prior to the performance of any trial activities. 2. Patients, males and females, ≥ 18 years of age at the time of signing the informed consent. 3. Patients with Karnofsky performance status (KPS) index \> 60% (Appendix 5). 4. Diagnosis of Grade 2-4 astrocytoma, IDH-mutated according to the 2021 WHO classification. 5. Patients must have confirmed ATRX mutation (IHC or NGS sequencing) and p53 mutation (NGS sequencing). Evaluation of CDKN2A also is required by FISH or NGS. 6. Patients must have progressive disease and evaluable disease according to RANO 2.0 criteria. All patients should have MRI contrast enhancement disease. 7. Patients must have undergone previous standard treatment with radiotherapy and chemotherapy (procarbazine, lomustine and vincristine \[PCV\] or temozolomide \[TMZ\]). 8. Stable corticosteroid doses during the 2 weeks previous to the first dose of tuvusertib, maximum dose of dexamethasone 4 mg/day or equivalent. 9. Adequate hematologic, hepatic and renal function as follows: 1. Platelet count ≥ 100,000/mm3, 2. Hemoglobin ≥ 9.0 g/dL, 3. Absolute neutrophil count ≥ 1,500/μL with no growth factor treatment within the last 14 days, 4. Total bilirubin level ≤ 1.5 × upper limit of normal (ULN) (if Gilbert's Syndrome may have total bilirubin \> 1.5 × ULN), 5. Aspartate aminotransferase (AST) level ≤ 3 × ULN, and an alanine aminotransferase (ALT) level ≤ 3 × ULN. 6. Serum creatinine ≤ 1.5 × ULN. If serum creatinine is \> 1.5 × ULN, creatinine clearance needs to be ≥ 50 mL/min, as estimated by Cockcroft-Gault 10. Contraceptive use by males or females will be consistent with local regulations on contraception methods for those participating in clinical studies. 11. Patients able to take oral medications. 12. Willingness and ability of patients to comply with the protocol for the duration of the study including undergoing treatment as well as availability for scheduled visits and examinations including follow-up. Exclusion Criteria: 1. Patients with radiographic recurrence without contrast enhancement by MRI. 2. Leptomeningeal dissemination and/or extracranial metastases. 3. Patients who received more than 1 previous systemic line of treatment for astrocytoma. 4. Patients who received previous treatment with bevacizumab. 5. Persistence of AEs related to any prior treatments that have not recovered to Grade ≤ 1 unless AEs are clinically nonsignificant (e.g. alopecia) and/or stable on supportive therapy in the opinion of the Investigator. 6. No prior ATR inhibitor and/or CHK1 inhibitor. 7. Concurrent treatment with a non permitted drug/intervention: 1. Prohibited concomitant medication, as listed in Section 7.8. 2. Anticancer treatment within 30 days or 5 half-lives, whichever is shorter, prior to Day 1 of study intervention (6 weeks for nitrosoureas or mitomycin C). 3. Prior palliative radiotherapy to metastatic lesion(s) is permitted provided it was completed ≥ 12 weeks prior to study intervention administration and participants have recovered from all related radiotherapy toxicities to Grade ≤ 1. 4. Another investigational drug within 30 days or 5 half-lives, whichever is shorter, prior to start of tuvusertib administration. 5. Increasing dose of corticoids. 6. Received hematopoietic growth factor (e.g., granulocyte colony-stimulating factor, erythropoietin) within 14 days prior to the first dose of tuvusertib. 8. Significant cardiac disease: 1. Unstable angina, myocardial infarction, congestive heart failure ≥ stage II) or a coronary revascularization procedure within 180 days of study entry. 2. Calculated QTc average (using the Fridericia correction calculation) of \> 450 msec for males and \> 470 msec for females. 3. Uncontrolled hypertension. 9. Active and/or uncontrolled infection. The following exceptions apply: 1. Participants with HIV infection are eligible if they are on effective antiretroviral therapy with undetectable viral load within 6 months, provided there is no expected drug-drug interaction 2. Participants with evidence of chronic HBV infection are eligible if the HBV viral load is undetectable on suppressive therapy (if indicated), and if they have ALT, AST, and total bilirubin levels \< ULN, and provided there is no expected drug-drug interaction 3. Participants with a history of HCV infection are eligible if they have been treated and cured. For participants with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load, and if they have ALT, AST, and total bilirubin levels \< ULN. 11\. Treatment with live or live attenuated vaccine within 30 days of dosing. 12\. Known hypersensitivity to the components of tuvusertib. 13\. Major surgery (as deemed by the Investigator) for any reason, except diagnostic biopsy, within 4 weeks of the study intervention and/or if the patient has not fully recovered from the surgery within 4 weeks of the study intervention.