A Study to Assess the Safety and Tolerability of AZD1390 Given With Radiation Therapy in Patients With Brain Cancer

This first time-in patients (FTIP), open-label, multicentre study of AZD1390 will be conducted in the United States, the United Kingdom and Japan. It consists of three treatment arms: Arm A, B, C. The Japan dose confirmation part (Japan part) is a sub-study of Arm A. Sites from Japan will only participate in the Japan part. This Phase 1 study will assess safety and tolerability of AZD1390 in combination with radiation therapy (RT) in brain malignancies. The combination cohorts have been designed to assess escalating cumulative doses of AZD1390 in settings with 3 different radiation treatment regimens: * Arm A: 35 Gy over 2 weeks with intensity-modulated radiation therapy (IMRT) in patients with recurrent Glioblastoma Multiforme (GBM). Arm A will also include the food effect cohort * Arms B: 30 Gy over two weeks with whole brain radiation therapy (WBRT)/ partial brain radiation therapy (PBRT) in patients with brain metastases. \*\*Arm B has now closed to recruitment\*\* * Arm C: 60 Gy over 6 weeks (IMRT) in patients with primary GBM Each arm provides standard of care RT for the disease setting indicated with the experimental agent being administered in dose escalating cohorts.