• Provision of formalin-fixed paraffin embedded tissue sample from primary or metastatic disease

• Karnofsky Performance Score of ≥60.

• Additional Inclusion Criteria Specific for Arm A and Japan:

‣ Histologically proven diagnosis of GBM. Patients who have had RT for low-grade glioma (LGG) or grade 3 glioma and have subsequently relapsed to histologically confirmed GBM can be considered

⁃ A radiological diagnosis of recurrent/relapsed or progressive disease according to RANO criteria.

⁃ Completion of first-line radiation at least 6 months prior to Cycle 1 Day 1.

⁃ Patients with tumor-induced seizures must be well controlled on a stable anti-epileptic treatment

⁃ Willing to receive anti-epileptic prophylaxis for the duration of study drug administration.

• Additional Inclusion Criteria Specific for Arm B:

∙ \*\*Arm B has now closed to recruitment\*\*

• Histologically proven diagnosis of solid tumor malignancy and Magnetic Resonance (MR) imaging documenting brain lesions.

• Not eligible for Stereotactic Radiosurgery (SRS) treatment of brain tumor.

• Patient has not received any previous brain RT to the area that is to be irradiated. Prior PBRT may be allowed if there is not significant overlap between the prior and new radiation fields.

• Non-CNS malignant disease must be sufficiently controlled so that patients can be without additional systemic therapy for the required washout period before starting therapy until 5 days after the end of RT. Required washout period before starting the first dose of AZD1390 (Cycle 1) is 28 days for immune checkpoint inhibitors and 7 days for all other agents

• Not received radiation to the lung fields within the past 8 weeks.

• No history of seizures related to the brain metastases or LMD.

• Receiving PBRT (rather than WBRT) during Cycle 1 as standard of care for brain metastases

• • Additional Inclusion Criteria Specific for Arm C:

• Histologically proven primary diagnosis of GBM with unmethylated O6-methylguanine-DNA methyltransferase (MGMT). Grade 4 astrocytoma or histology with molecular features of GBM can be considered.

• Determination of MGMT promoter status by methylation-specific polymerase chain reaction (PCR) or pyrosequencing per local institutional guidelines is required to assess eligibility for this Arm.

• Patients will have to undergo mutational testing for Isocitrate dehydrogenase 1 (IDH1) on a tumor specimen before entering study. Patients are eligible for Arm C regardless of their IDH1 mutational status.

• No history of uncontrolled seizures after surgery for primary GBM (despite adequate antiepileptic therapy) or with need for concurrent administration of more than 2 antiepileptic drugs.

• Willing to receive anti-epileptic prophylaxis for the duration of study drug administration

∙ Additional Inclusion criteria for Food Effect Assessment (Arm A):

• For the fed assessment portion: fast overnight (for at least 10 hours) prior to consuming a high-fat meal consisting of approximately 800 to 1000 calories, with around 54% of the calories coming from fat.

• For the fasted assessment portion: fast overnight (for at least 10 hours prior to dosing) and until 4 hours after dosing.

∙ \*Note: the optional food effect assessment is currently open to enrolment\*