• 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