This Study is a Phase II Study of AZD6738 in Combination With Durvalumab in Patients With Solid Tumor (Cohort A (N=30): GC Who Have Failed Secondary Chemotherapy Treatments Regimen; Cohort B (B=30): Melanoma Patients Who Have Failed to IO)

Exclusion Criteria

• •1. Diagnosis of ataxia telangiectasia.
• •2. Any previous treatment with ATR inhibitors, DNA -damage repair inhibitors
• •3. Any gastrointestinal condition that would preclude adequate abosrportion of AZD6738 including but not limited to inability to swallow oral medication, refractory nausea and vomiting, chronic gastrointestinal diseases or previous significant bowel resection, intestinal obstruction or CTCAE grade 3 or grade 4 upper GI bleeding within 4 weeks before the enrollment.
• •4. Active or prior documented autoimmune or inflammatory disorders (including IBD\[e.g. Chohn's disease, ulcerative colitis or diverticulitis\], SLE, sarcoidosis syndrome, tuberculosis, Wegener syndrome, myasthenia gravis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, history of primary immunodeficiency or HIV infection, known hepatitis B or hepatitis C infection, history of organ transplant that requires use of immunosuppressives, glomerulonephritis, nephritic syndrome, Fanconi Syndrome or renal tubular acidosis within the past 2 years prior to the start of treatment. The following are exceptions to this criterion:
• •* Subjects with vitiligo or alopecia, hypothyroidism (eg, following Hashimoto syndrome) stable on hormone replacement or psoriasis not requiring systemic treatment; patients with coeliac disease controlled by diet alone and patients without active disease in the last 5 years may be included after consultation with Chief Investigator.
• •5. Untreated central nervous system (CNS) metastatic disease, leptomeningeal disease, or cord compression. Note: Subjects previously treated for CNS metastases that are asymptomatic, radiographically and neurologically stable for at least 4 weeks and do not require corticosteroids (of any dose) for symptomatic management for at least 4 weeks prior to the first dose of treatment are not excluded.
• •6. Patients with second primary cancer, except: adequately treated non-melanoma skin cancer, curatively treated in-situ cancer of the cervix, or other solid tumours curatively treated with no evidence of disease for ≤3 years.
• •7. Current or prior use of immunosuppressive medication within 4 weeks prior to the first dose of durvalumab, with the exceptions of intranasal, topical, and inhaled corticosteroids; systemic corticosteroids at physiologic doses not to exceed a dose \> 10 mg prednisone / day or equivalent)
• •8. Patient was in receipt of any live attenuated vaccination within 30 days prior to study entry or within 30 days of receving study therapy.
• •9. Receiving or having received, concomitant medications, herbal supplements, and/or foods that significantly modulate P450 3A4 (CYP3A4) or Pgp activity (washout periods of 5 half-lives). Note these include common azole antifungals, macrolide antibioics and other medications.
• •10. Patient with any of the following cardiac criteria:
• •* Mean QT interval corrected for heart rate (QTc) ≥ 470 ms calculated from 3 electrograms (ECGs) using Friderecia's correction
• •* Any clinciallly important abnormalities in fhythm, conduction or morphology of resting ECG e.g. complete left bundle branch block , third degree heart block, second degree heart block.
• •* Any factors that increae 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 or concomitant medication known to prolong the QT interval
• •* Uncontrolled hypotension: systolic BP \< 90 mmHg and/or diastolic BP 60 mmHg or clinically relvant orthostatic hypotension, including a fall in blood pressure of \> 20 mmHg
• •* Atrial fibrillation with a ventricular rate \>100 bpm on ECG at rest
• •* Symptomatic heart failure (NYHA grade II-IV)
• •* Known reduced LVEF \< 55%
• •* Prior or current cardiomyopathy
• •* Severe valvular heart disease
• •* Uncontrolled angina (Canadian Cardiovascular Society grade II-IV despite medical therapy)
• •* Stroke or transient ischaemic attack in the last 6 months prior to screening
• •* Acute coronary syndrome within 6 months prior to starting treatment
• •11. Ophthalmological conditions as follows:Intra-ocular pressure \>21 mmHg, or uncontrolled glaucoma (irrespective of intra-ocular pressure), Current or past history of central serous retinopathy or retinal vein occlusion
• •12. Any evidence of severe or uncontrolled systemic disease, including active infection (requiring antibiotics, antifungals or antivirals), diabetes type I and II, uncontrolled seizures, bleeding diatheses, severe COPD, severe Parkinson's disease.
• •13. Any unresolved toxicity NCI CTCAE Grade ≥2 from previous anticancer therapy with the exception of alopecia, vitiligo, Major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose of IP. Note: Local surgery of isolated lesions for palliative intent is acceptable.
• •14. Female patients who are pregnant or breastfeeding or male or female patients of reproductive potential who are not willing to employ effective birth control from screening to 90 days after the last dose of durvalumab monotherapy.
• •15. Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients.