Study to Assess the Safety and Preliminary Efficacy of AZD0156 at Increasing Doses Alone or in Combination With Other Anti-cancer Treatment in Patients With Advanced Cancer

The purpose of this study is to determine whether AZD0156 is safe, what is the best dose to give, and how it is processed by the body when given alone or in combination with other agents. The study will also collect some initial information about how effective it is.

The study will consist of a number of study modules, each evaluating the safety and tolerability of AZD0156 with a specific combination agent. The combination option may require an initial monotherapy dose escalation to gain an understanding of pharmacokinetics, safety and tolerability before initiating dose escalation in combination. An oral formulation of AZD0156 will be used.

Module 1 explores AZD0156 in combination with olaparib Module 2 explores AZD0156 in combination with irinotecan/FOLFIRI Additional modules may be added to explore AZD0156 as a monotherapy or in combination with other agents and may be in different tumour types.

Expansion cohorts may enroll additional patients to explore further the safety, tolerability, pharmacokinetics and biological activity at selected dose(s) or alternate dosing schedules, and to get a preliminary assessment of efficacy .

Module 1 includes an expansion cohort in locally advanced/metastatic tumours including but not limited to gastric adenocarcinoma Module 2 includes an expansion cohort in colorectal cancer

Eligibility Criteria:
Inclusion criteria for all parts of the study

* Confirmation of locally advanced/metastatic cancer. Refractory or resistant to standard therapy, or have no effective standard
* Aged at least 18 yrs
* Reasonable health (performance status 0 or 1), stable over the previous 2 weeks
* Females who can have children must use contraception; have a negative pregnancy test, \& not be breast feeding
* Sexually active male patients must use contraception for duration of study and for 3 months afterwards Inclusion criteria for Part B only
* Tumour(s) that can be measured by CT or MRI, at least 1cm in size Inclusion Part B
* Confirmation of metastatic/locally advanced cancer of specific tumour type which failed to respond to standard treatments Exclusion criteria for all parts of the study
* Prior treatment with an ATM inhibitor
* Past medical history of an inflammatory type(interstitial) lung disease or current inflammatory lung disease
* Radiotherapy within the last 4 weeks, except palliative radiotherapy for bone pain relief
* Prior treatment with drugs that may cause lung damage
* Poor of lung function
* History/presence of muscle weakness or abnormal blood tests relating to muscle function
* Cancer affecting the spinal cord and/or brain unless asymptomatic and stable
* Any evidence of severe or uncontrolled diseases, active bleeding,kidney transplant, or active infection including liver infections (hepatitis B, hepatitis C) and human immunodeficiency virus (HIV).
* Evidence of severe lung infections
* Receiving, or having received during the four weeks prior to starting study treatment other chemotherapy treatment for your cancer
* Treatment with certain doses of steroids during the two weeks prior to starting study treatment
* A known sensitivity to AZD0156 or any of its components
* Treatment with any unapproved medicine within 28 days prior to starting study treatment
* Receiving, or having received medications, herbal supplements and/or foods that significantly affect how your liver works
* Low numbers of certain blood cells
* If your liver and kidney aren't working normally
* If your heart isn't working normally or you have a strong family history of certain heart diseases
* Other cancers within the past 3 years, except for certain types of cervical and skin cancers
* Sickness and vomiting, digestive diseases or previous significant bowel removal
* Patients with uncontrolled fitting
* Infections requiring treatment
* Other severe and/or uncontrolled medical conditions in addition to your cancer
* A blockage in your digestive system or severe bleeding from the stomach within 4 weeks before your take medication on the stuy
* Patients with acute leukaemia or certain bone marrow diseases
* Patients with a known sensitivity to olaparib or its components (Module 1), or components of FOLFIRI (Module 2)
* Any previous treatment with drugs that work like olaparib. (Module 1 Only)