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

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