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

An oral formulation of ceralasertib will be used. In Module 2 Part A1, patients will receive a single dose of ceralasertib on Day 1, followed by 4 to 6 days washout, before multiple dosing.

An oral formulations of ceralasertib and olaparib will be used. In Module 2 Part A2, patients will receive either a single or twice daily dose of ceralasertib followed by 4 to 6 days washout, before multiple dosing with ceralasertib and olaparib. In Module 2 Part B, patients will receive ceralasertib and olaparib at the dose, frequency and schedule recommended from Module 2 Part A2. Cycle 0 may be omitted at the discretion of the sponsor.

An oral formulation of ceralasertib will be used. Durvalumab is given via IV infusion. In Module 3 Part A, patients will receive an initial single dose of ceralasertib on Day 1, followed by multiple dosing in combination with durvalumab. In Module 3 Serial Tumour Biopsy Extension and Part B expansion cohorts, patients will receive ceralasertib at the dose, frequency and schedule recommended from Module 3 Part A, in combination with durvalumab.

Module 4 Part A and Module 4 Part B Cohort 3: During C0, patients will receive ceralasertib monotherapy orally once a day on 3 non-consecutive days and ceralasertib twice a day on 5 consecutive days. After the patients have completed C0 (Part A) they may transition to Module 4 Part B cohort 3 where they will continue to receive ceralasertib monotherapy

"Module 4 Part B Cohort 1:~After completion of Part A (C0), the patient may transition to Part B and be allocated to receive ceralasertib in combination with olaparib as decided by the investigator."

"Module 4 Part B Cohort 2:~After completion of Part A (C0), the patient may transition to Part B and be allocated to receive ceralasertib in combination with durvalumab as decided by the investigator."

An oral formulations of ceralasertib and AZD5305 will be used. In Module 5 Part A, patients will receive a single dose of ceralasertib on cycle 0 Day 1 as per dose level cohort. In Module 5 Part B, patients will receive ceralasertib and AZD5305: C1 onwards (as per dose level cohort allocated).

An oral formulation of ceralasertib will be used. In Module 1 Part A, patients will receive a single dose of ceralasertib on Day 1, followed by multiple dosing in combination with carboplatin. A maximum of 6 cycles (21 days per cycle) of treatment will be given. In Module 1 Part B, patients will receive ceralasertib and carboplatin at the dose, frequency and schedule recommended from Module 1 Part A.