AZD9150 Plus Durvalumab Alone or in Combination With Chemotherapy in Patients With Advanced, Solid Tumours and in Patients With Non-Small-Cell Lung Cancer

Inclusion Criteria

• Inclusion Criteria Subjects are eligible to be included in the study only if all of the following inclusion criteria and none of the exclusion criteria apply. 1. Signed and dated informed consent. For inclusion in the optional pharmacogenetic research, patients must provide informed consent for the genetic sampling and analyses. 2. ≥ 18 years of age. 3. An Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1. 4. Minimum life expectancy of 12 weeks 5. Part A of the study will include patients that have histological confirmation of a solid malignancy [other than Hepatocellular Carcinoma (HCC)] that is refractory to standard therapy or for which no standard of care regimen currently exists. 6. Part D of the study will include patients with histological confirmation of a solid malignancy (other than HCC) that are refractory to standard therapy of for which no standard of care regimen currently exists. 7. Willing to undergo mandatory biopsy at screening and on treatment. Part A only: the first 3 subjects in each arm are exempt from this requirement. Patients in Part D are exempt from this biopsy requirement. 8. At least one lesion, not previously irradiated, that can be accurately measured at baseline as ≥10 mm in the longest diameter (except lymph nodes that must have short axis ≥15 mm) with computerised tomography (CT) or magnetic resonance imaging (MRI) that is suitable for accurate repeated measurements. 9. Females should be using adequate contraceptive measures, should not be breast feeding, and must have a negative pregnancy test prior to start of dosing if of child-bearing potential or must have evidence of non-child-bearing potential by fulfilling one of the following criteria at screening: - Post-menopausal defined as aged more than 50 years and amenorrhoeic for at least 12 months following cessation of all exogenous hormonal treatments - Women under 50 years old would be considered postmenopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and with luteinising hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution - Documentation of irreversible surgical sterilisation by hysterectomy, bilateral oophorectomy, or bilateral salpingectomy, but not tubal ligation. 10. Male patients must be surgically sterile or using an acceptable method of contraception (defined as barrier methods in conjunction with spermicides) for the duration of the study (from the time they sign consent) and for 20 weeks after the last dose of study treatments. Exclusion Criteria Patients should not enter the study if any of the following exclusion criteria are fulfilled. 1. Involvement in the planning and/or conduct of the study (applies to AstraZeneca and/or Sarah Cannon Development Innovations staff and/or staff at the study site). 2. Previous enrolment in the present study. 3. Herbal preparations are not allowed throughout the study. These herbal medications include but are not limited to St. John's wort, kava, ephedra (mahung), gingko biloba, dehydroepiandrosterone (DHEA), yohimbe, saw palmetto and ginseng. Patients should stop using herbal medications 7 days prior to the first dose of study treatment. 4. Brain metastases or spinal cord compression unless asymptomatic and not requiring steroids for at least 14 days prior to start of study treatment. 5. With the exception of alopecia and haemoglobin (Hb) ≥ 9 mg/dL and < 10 mg/dL, any unresolved toxicities from prior therapy CTCAE Grade > 1 at the time of starting study treatment. 6. Active interstitial lung disease (ILD)/pneumonitis or a prior history of ILD/pneumonitis requiring treatment with steroids. 7. Patients receiving any concurrent chemotherapy, radiotherapy, immunotherapy, or biologic, or hormonal therapy for cancer. - Concurrent use of hormones for noncancer-related conditions (e.g., insulin for diabetes and hormone replacement therapy) is acceptable. The dose of systemic corticosteroids must not exceed 10 mg of prednisone equivalent. - Patients in Part A and Part D with radically-treated prostate cancer may continue androgen deprivation therapy (ADT). 8. Patients must have completed any previous cancer-related treatments before enrolment. The following intervals between the end of the prior treatment and first dose of study drug must be observed: - Port-a-cath placement: no waiting is required - Minor surgical procedures (as defined by the Medical Monitor): 7 postoperative days - Major surgery (as defined by the Medical Monitor): ≥4 weeks - Radiotherapy: ≥4 weeks (patients who receive palliative radiation for nontarget tumour lesions need not be subjected to this washout period and can be enrolled immediately) - Chemotherapy: ≥ 21 days or 5 half-lives (whichever is longer) from the first dose of study drug - Immunotherapy and/or anticancer therapy with agents including mAbs ≥4 weeks - Current or prior use of immunosuppressive medication within 14 days before first dose of durvalumab The following are exceptions to this criterion: - Use of intranasal, inhaled, topical corticosteroids, local steroid injections (e.g., intra articular injections) - Systemic corticosteroids at physiologic doses below 10 mg/day of prednisone or equivalent is permitted - Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication) are permitted 9. For Part A and Part D patients who have received more than 3 prior cytoreductive chemotherapy regimens. 10. Has active or prior documented autoimmune disease within the past 2 years with the exceptions of vitiligo, Graves' Disease, and/or psoriasis not requiring systemic treatment 11. Has active or prior documented inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis) 12. Has a history of primary immunodeficiency 13. Has undergone an organ transplant that requires use of immunosuppressive treatment 14. Any of the following cardiac criteria: - Mean resting corrected QT interval (QTc) calculated using Fridericia's formula (QTcF) of >450 msec for males and >470 msec for females obtained from 3 electrocardiograms (ECGs) taken over 5 minutes - Any clinically important abnormalities in rhythm, conduction or morphology of a resting ECG, e.g., complete left bundle branch block, third degree heart block, that in the opinion of the Investigator renders the patient unsuitable for participation in the study - Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalaemia, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years-of-age - Any concomitant medication with known or possible risk of prolonging the QT interval. 15. Inadequate organ and marrow function as demonstrated by any of the following laboratory values. Transfusions intended to elevate any parameters below solely for the intent of meeting study eligibility are not permitted. - Leukocytes <3.0 x 10(exp 9)/L - Absolute neutrophil count <1.5 x 10(exp 9)/L - Platelet count <100 x 10(exp 9)/L - Haemoglobin <90 g/L - Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >2.5 times the upper limit of normal (ULN) if no demonstrable liver metastases or >5 times ULN in the presence of liver metastases - Total bilirubin >1.5 times ULN if no liver metastases or 3 times ULN in the presence of liver metastases or documented Gilbert's Syndrome (unconjugated hyperbilirubinaemia) - Creatinine outside normal limits OR, if creatinine outside normal limits, a creatinine clearance <60 mL/min (measured by 24-hour urine collection or calculated by Cockcroft and Gault equation (Cockcroft and Gault 1976). 16. Has a history of allergic reactions attributed to the study treatments (AZD9150 or durvalumab), assigned chemotherapy agents, their compounds, or agents of similar chemical or biologic composition (e.g., antibody therapeutics) 17. Suffers from a comorbidity that in the opinion of the Investigator or Medical Monitor renders the patient unsuitable for participation in the study. Such comorbidity may include, but is not limited to, uncontrolled intercurrent illness such as active infection, severe active peptic ulcer disease or gastritis, myocardial infarction within 6 months before entry, congestive heart failure, symptomatic congestive heart failure, active cardiomyopathy, unstable angina pectoris, cardiac arrhythmia, uncontrolled hypertension, or psychiatric illness/social situations that would limit compliance with study requirements. 18. As judged by the Investigator, has any evidence of severe or uncontrolled diseases, or has an active viral infection of human immunodeficiency virus (HIV), human papilloma virus (HPV), hepatitis B virus (HBV), and/or hepatitis C virus (HCV)]. 19. Active infection including tuberculosis (clinical evaluation that included clinical history, physical examination and radiographic findings, and tuberculosis testing in line with local practice). 20. Has received a live attenuated vaccine within 28 days before the first dose of study drug 21. Judgment by the Investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions, and requirements.