A Modular Phase I/IIa, Open-label, Multi-centre Study to Assess the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Preliminary Efficacy of Ascending Doses of AZD9574 as Monotherapy and in Combination with Anti-cancer Agents in Patients with

The main purpose of this study is to determine a dose of AZD9574 that is safe and tolerable (does not cause side effects that could prevent people from taking the drug) when given alone or in combination with temozolomide. The study will also evaluate how much of the study drug is in your blood at various times. In addition, the action of the study drug will be evaluated by measuring specific chemicals in the blood. All parts of this study are experimental which means AZD9574 is not approved by the U.S. Food and Drug Administration (FDA). This is the first time AZD9574 has been tested in people. AZD9574 is a type of drug known as a PARP inhibitor. PARP inhibitors are a type of targeted cancer drugs. PARP helps damaged cells to repair themselves, including cancer cells. As a cancer treatment, PARP inhibitors may stop the PARP from doing its repair work in cancer cells resulting in the cancer cells dying.

Are you Eligible? (Inclusion Criteria)

• Must be 18 years old or older - Female participants must have a negative pregnancy test result at screening and prior to each cycle administration of AZD9574. - Module 1: At least one measurable and/or non-measurable lesions that can be assessed at the study start and can have multiple assessments by CT or MRI scans during the study. - Module 2: Must not have a known hypersensitivity to TMZ, known hypersensitivity to dacarbazine or known history of allergic reactions associated with drugs similar to AZD9574.