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

Required: MGMT unmethylated promoter

primary diagnosis of GBM with unmethylated O6-methylguanine-DNA methyltransferase (MGMT). 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.

Allowed: IDH1 mutational testing required

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.

Must have received: radiation therapy — first-line

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

Cannot have received: chemotherapy

Administration of chemotherapy or any investigational drug in the 28 days or carmustine (CCNU) or lomustine (BCNU) in the 6 weeks prior to receiving the first dose of treatment in Arms A and C.

Cannot have received: immune checkpoint inhibitor

Administration of checkpoint inhibitors within 28 days prior to first dose of treatment and any other agent within 7 days of beginning study treatment in Arm B.

Cannot have received: hormonal therapy

Exception: Hormonal therapies are allowed during study treatment for patients in Arm B.

Hormonal therapies are allowed during study treatment for patients in Arm B.

Cannot have received: pneumotoxic drugs (busulfan, bleomycin)

Exception: If prior therapy in lifetime, then excluded if history of pulmonary toxicities from administration.

Prior treatment with pneumotoxic drugs, e.g. busulfan, bleomycin, within the past year. If prior therapy in lifetime, then excluded if history of pulmonary toxicities from administration.

Cannot have received: nitrosourea (carmustine, lomustine)

Exception: Patients who have received treatment with nitrosoureas (e.g., carmustine, lomustine) in the year before study entry without experiencing lung toxicity are allowed on study.

Patients who have received treatment with nitrosoureas (e.g., carmustine, lomustine) in the year before study entry without experiencing lung toxicity are allowed on study.

Cannot have received: ATM inhibitor with concurrent RT

Has previously received ATM inhibitor with concurrent RT