A Study to Assess the Safety, Tolerability and Anti-tumour Activity of Ascending Doses of Selumetinib in Combination With MEDI4736 and Selumetinib in Combination With MEDI4736 and Tremelimumab in Patients With Advanced Solid Tumours

• 1. Written informed consent and any locally-required authorization (eg, Health Insurance Portability and Accountability Act in the US, EU Data Privacy Directive in the EU) obtained from the patient prior to performing any protocol-related procedures, including pre-screening and screening evaluations 2. Age ≥18 years at time of study entry 3. Histological or cytological confirmation of locally advanced (stage IIIB) or metastatic (stage IV) solid tumours refractory to standard therapy or for which no standard therapy exists 4. World Health Organisation Eastern Cooperative Oncology Group (ECOG) performance status 0-1 with no deterioration over the previous 2 weeks and minimum life expectancy of 12 weeks 5. At least 1 lesion, not previously irradiated, that can be accurately measured at baseline as ≥10 mm in the longest diameter (except lymph nodes which must have short axis ≥15 mm) with computed tomography (CT) or magnetic resonance imaging (MRI) and which is suitable for accurate repeated assessment as per Response Evaluation Criteria in Solid Tumours (RECIST criteria v1.1) 6. Female patients and males with partners of childbearing potential should be using highly effective contraceptive measures. Females should not be breastfeeding and must have a negative pregnancy test prior to start of dosing if of childbearing potential or must have evidence of non-childbearing potential by fulfilling 1 of the criteria below at screening.
• Postmenopausal defined as aged more than 50 years and amenorrhoeic for at least 12 months following cessation of all exogenous hormonal treatments
• Women \<50 years old would be considered postmenopausal if they have been amenorrheic for the past 12 months or more following cessation of exogenous hormonal treatments. The levels of luteinising hormone (LH) and follicle stimulating hormone (FSH) must also be in the postmenopausal range (as per the institution)
• Documentation of irreversible surgical sterilisation by hysterectomy and / or bilateral oophorectomy and/or bilateral salpingectomy but not tubal ligation 7. Male patients should be willing to use barrier contraception ie, condoms plus spermicide 8. Mandatory provision of tumour tissue sample available at study entry for exploratory biomarker research. Cytology samples for this exploratory biomarker research will not be acceptable 9. Patients must have mCRC and, if MSI status is known, non-high MSI status. MSI status will be evaluated based on previous results of local MSI testing, if available. Patients with known MSI-high status will be excluded; patients with MSS, MSI-low, or unknown MSI status may be enrolled

Patients must not enter the study if any of the following