Ascending Doses of Ceralasertib in Combination With Chemotherapy and/or Novel Anti Cancer Agents

Inclusion Criteria

• Principal Inclusion criteria: - Aged at least 18 - The presence of a solid malignant tumour that is not considered appropriate for further standard treatment - Module 2 Part B study expansions, and Module 3: patients must have a tumour at least 1 cm in size that can be measured using a CT or MRI scan - Module 2 Part B All (except B5): No previous treatment with PARP inhibitor. - Module 2 Part B1 Study expansion: advanced gastric adenocarcinoma (including GEJ) patients with ATM deficient tumours - Module 2 Part B2 Study expansion: advanced gastric adenocarcinoma (including GEJ) patients with ATM proficient tumours - Module 2 Part B3 Study expansion: Second or thrid line HER2 negative breast cancer - Module 2 Part B4 Study expansion: Second or third line triple negative breast cancer (TNBC) - Module 2 Part B5 Study expansion: BRCAm or RAD51C/Dm or PALB2m or HRD positive status ovarian cancer patient who are Platinum Sensitive Relapsed and have previously progressed on a licensed PARPi - Module 3: advanced recurrent or metastatic non-small cell lung cancer, or head and neck squamous cell carcinoma - Module 4: any advanced solid tumours except gastric, gastro-oesophageal, oesophageal or colorectal cancer with a small bowel resection - Module 4: Ability to comply with an overnight fast of at least 10 hours prior to dosing and 4 hours after dosing as mandated, and ability to eat a high fat meal as mandated - Module 5 All: Ovarian fallopian tube or primary peritonial cancer, previous treatment with PARP inhibitor, platinum-sensitive relapsed ovarian cancer - Module 5 Part B: known or suspected BRCA mutation, PALB2 mutation, RAD51C/D mutation or HRD positive status Principal exclusion criteria - A diagnosis of ataxia telangiectasia - Prior exposure to an ATR inhibitor - Bad reaction to ceralasertib - Module 2: Contra-indicated for treatment with olaparib - Module 3: Contra-indicated for treatment with durvalumab - Module 4: Mean resting corrected QT interval (QTc) >470 msec or history of familial long QT syndrome. - Module 4: Patients with type I or type II diabetes - Module 5: Known hypersensitivity to PARP including AZD5305