Study of AZD9574 as monotherapy and in combination with anti-cancer agents in participants with advanced solid malignancies - CERTIS1

Exclusion Criteria

• - Major surgery within 4 weeks of the first dose of study intervention.
• - Radiotherapy with a wide field of radiation within 4 weeks or radiotherapy with a limited field of radiation for palliation within 2 weeks of the first dose of study intervention.
• - With the exception of alopecia, any unresolved toxicities from prior therapy greater than Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 at the time of starting study intervention.
• - Any known history of persisting severe pancytopenia due to any cause.
• - Spinal cord compression unless asymptomatic, treated and stable and not requiring continuous corticosteroids at a dose of > 10 mg prednisone/day or equivalent for at least 4 weeks prior to start of study intervention.
• - History of uncontrolled seizures or with need for concurrent administration of more than 2 antiepileptic drugs, or history of epileptic disorder or any seizure history unrelated to tumour.
• - History of severe brain injury or stroke.
• - Any evidence of severe or uncontrolled systemic diseases including active bleeding diatheses, active infection including hepatitis B, hepatitis C and human immunodeficiency virus (HIV).
• - Uncontrolled intercurrent illness within the last 12 months.
• - Any known predisposition to bleeding.
• - Patients with myelodysplastic syndrome (MDS)/acute myeloid leukaemia (AML) or with features suggestive of MDS/AML.
• - Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the
• formulated product or previous significant bowel resection that would preclude adequate absorption of AZD9574.
• - Known allergy or hypersensitivity to investigational product(s) or any of the excipients of the investigational product(s).
• - Known contra-indication to gadolinium-enhanced Magnetic Resonance Imaging (MRI) or, if applicable, not able to be maintained on a stable or decreasing dose of corticosteroid regimen (no increase for 7 days) prior to the baseline MRI.
• - Any concurrent anti-cancer therapy or concurrent use of prohibited medications.
• Module 1:
• Part A:
• - Participants that have received > one prior line of therapy in any setting with a PARPi-based regimen.
• - Participants with an INR >1.5 unless the patient is receiving non-vitamin K antagonist oral anticoagulants.
• - Participants with LMD unless the LMD is of low volume or is previously irradiated and the participant is asymptomatic from the LMD.
• Part B:
• - Participants with an International Normalised Ratio (INR) >1.5 unless the patient is receiving non-vitamin K antagonist oral anticoagulants.
• - Participants with LMD are excluded unless the LMD is of low volume or is previously irradiated and the participant is asymptomatic from the LMD.
• Module 2:
• - Participants who have received a PARPi previously.
• - Known hypersensitivity to TMZ or dacarbazine or known history of allergic reactions attributed to compounds of similar chemical or biologic composition to AZD9574.
• - Participants who have received > 1 prior line of alkylating chemotherapy regimen.
• - Participants who had previously experienced Grade 4 haematological toxicities or Grade 3 neutropenia associated with infections, or Grade 3 thrombocytopenia with clinically significant bleeding during prior alkylating chemotherapy.
• - Participants who have received bevacizumab within the last 6 months.
• - Not requiring continuous corticosteroids at a dose of >10 mg prednisone/day or equivalent for at least 4 weeks prior to start of study intervention.