DURvalumab in Combination With S-488210/S-488211 vAccine in Non-muscle Invasive Bladder CancEr

Inclusion Criteria: 1. Histologically proven high risk non-muscle invasive bladder cancer (NMIBC) 2. Adequate archival tissue sample available for histological assessment (date sample taken must be within 6 months of planned start of treatment) 3. Predominant histologic component (\> 50%) must be urothelial (transitional cell) carcinoma 4. Bacillus Calmette-Guerin (BCG) unresponsive disease or are intolerant of BCG therapy 5. Refused or deemed clinically inappropriate for radical cystectomy 6. ≥18 years of age 7. Body weight \>30 kg 8. World Health Organisation (WHO) performance status 0-1 9. Must have undergone each of the following procedures within 8 weeks of registration: * Complete excision of all papillary disease (T1/TaHG) and demonstration of no muscle invasive disease in the resected specimens (muscle must be present in the tumour sample) * Bladder 'Mapping biopsies' taken * CT of the chest * CT Urogram or MRI of the abdomen and pelvis (if CT is not possible) 10. Adequate haematological status: * Haemoglobin ≥9.0 g/dL * Absolute neutrophil count ≥1.5 x 10\^9/L (≥150,000 per mm3) * Platelet count ≥100 x 10\^9/L (≥100,000 per mm3) * International Normalised Ratio (INR) ≤1.5 and Activated Partial Thromoplastin Time (APTT) ≤1.5 x Upper Limit Normal (ULN). NB: This applies only to patients who are not receiving therapeutic anticoagulation; patients receiving therapeutic anticoagulation should be on a stable dose. 11. Adequate liver function: * Total bilirubin ≤1.5 X ULN (\<3.0 x ULN for patients with Gilbert's syndrome) * Aspartate Aminotransferase (AST) or Alanine Aminotransferase (ALT) ≤2.5 x ULN 12. Adequate renal function: Measured creatinine clearance ≥40 mL/min or calculated creatinine clearance ≥40 mL/min using Cockcroft-Gault formula or by 24-hour urine collection for determination of creatinine clearance 13. Life expectancy of ≥6 months 14. Willing and able to give informed consent (which includes compliance with the requirements and restrictions listed in the patient information sheet (PIS) and in this protocol). NB: Consent must be obtained from the patient/legal representative prior to performing any protocol-related procedures, including screening evaluations. 15. Patients of child-bearing potential and male patients with female partners of child-bearing potential must agree to use highly effective contraception methods from date of consent, which must be continued for up to 90 days after last treatment administration. 16. Female patients must not be pregnant. There should be sufficient evidence of post-menopausal status or a negative serum pregnancy test for pre-menopausal female patients. 17. Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests and any other study procedures. Exclusion Criteria: 1. Any history of autoimmune or inflammatory disease including (any patients with a history of an autoimmune condition but without active disease in the last 5 years may be included only after consultation with the CI/TMG): * Inflammatory bowel disease (e.g. colitis or Crohn's disease) * Diverticulitis (with the exception of diverticulosis) * Systemic lupus erythematous (SLE) * Sarcoidosis syndrome * Wegener syndrome (granulomatosis with polyangitis, Grave's disease, rheumatoid arthritis, hypophysitis, uveitis, etc.) 2. Patients with prior allogeneic stem cell or solid organ transplantation 3. Patients who have had prior treatment with anti- PD-1, PD-L1 or CTLA-4 monoclonal antibody or other novel immune-oncology agent(s) 4. Active invasive malignancy in the previous 2 years excluding non-melanoma skin cancer 5. History of idiopathic pulmonary fibrosis (including pneumonitis), drug-induced pneumonitis, organizing pneumonia (i.e. bronchiolitis obliterans, cryptogenic organizing pneumonia) or evidence of active pneumonitis on screening chest CT scan (history of radiation pneumonitis in the radiation field is permitted) 6. Patients with interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected drug-related pulmonary toxicity 7. QTcF value of \>470 ms. If prolonged, this should be confirmed by 2 further ECGs each separated by at least 5 minutes. 8. Patients with the following risk factors for bowel perforation: * History of acute diverticulitis or intra-abdominal abcess in the last 3 years * History of mechanical GI obstruction or abdominal carcinomatosis 9. Any unresolved toxicity CTCAE Grade ≥2 from previous anti-cancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria. Patients with any irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab may be included only after consultation with the CI/TMG 10. Receipt of last dose of anti-cancer therapy (chemotherapy, immunotherapy, endocrine therapy, targeted therapy, biologic therapy, embolisation, monoclonal antibodies) within 30 days prior to first dose of trial treatment. NB: If sufficient washout time has not occurred due to the schedule or pharmacokinetic (PK) properties of an agent, a longer washout period will be required, as agreed by the Trial Management Group (TMG) and/or Chief Investigator (CI). 11. Treatment with any experimental drug within 30 days or 5 half-lives (whichever is longer) of the first dose of trial treatment 12. Concurrent enrolment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study 13. Any evidence of severe or uncontrolled systemic diseases or laboratory finding that in the view of the investigator makes it undesirable for the patient to participate in the trial 14. Received therapeutic oral antibiotics that cannot be discontinued at least 14 days prior to starting treatment or received intravenous (IV) antibiotics within 14 days prior to registration. NB: Patients receiving prophylactic antibiotics (e.g. for prevention of a urinary tract infection or COPD) are eligible 15. Any psychiatric or other disorder (e.g. brain metastases) that impacts the patients ability to give informed consent or comply with trial treatment and activities 16. History of leptomeningeal carcinomatosis 17. Active infection of tuberculosis (TB) (clinically evaluated in accordance with local guidelines, e.g. clinical history, examination and radiographic findings with or without TB testing as clinically indicated) 18. Patients must not have had systemic corticosteroid therapy (\>10 mg daily prednisolone equivalent) within 14 days prior to registration or concomitant use of other immunosuppressive medications. NB: The use of inhaled corticosteroids, physiologic replacement doses of glucocorticoids (i.e. for adrenal insufficiency) and mineralocorticoids (e.g. fludrocortisone) are allowed 19. Administration of a live, attenuated vaccine within 4 weeks prior to planned start of treatment or anticipation that such a live, attenuated vaccine will be required during the study 20. Evidence of significant uncontrolled concomitant disease that could substantially increase the risk of incurring adverse events (AEs), affect compliance with the protocol or interpretation of results, including significant liver disease (such as cirrhosis), uncontrolled hypertension, serious chronic gastrointestinal conditions associated with diarrhoea and uncontrolled major seizure disorder 21. Major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose of trial treatment. This does not include rigid cystoscopy and biopsies 22. Significant cardiovascular disease, such as: * New York Heart Association cardiac disease (Class II or greater) * Myocardial infarction within 3 months prior to registration * Unstable arrhythmias * Unstable angina 23. Patients with uncontrolled Type 1 diabetes mellitus. Patients controlled on a stable insulin regimen are eligible 24. Patients with uncontrolled adrenal insufficiency 25. Patients with active hepatitis infection (defined as having a positive hepatitis B surface antigen \[HBsAg\] test at screening) or hepatitis C. Patients with past hepatitis B virus (HBV) infection or resolved HBV infection (defined as having a negative HBsAg test and a positive antibody to hepatitis B core antigen \[anti-HBc\] antibody test) are eligible. Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV RNA 26. Known active primary immune deficiency, including but not limited to, uncontrolled human immunodeficiency virus (HIV) (detectable viral load) or acquired immunodeficiency syndrome (AIDS)-related illness 27. Women who are pregnant or breast feeding. Female or male patient of reproductive potential who is not willing to employ highly effective birth control from screening to 90 days after the last dose of trial treatment. 28. Known allergy or hypersensitivity to any of the investigational products or their excipients 29. Prior enrolment to, or treatment in a previous durvalumab clinical study, regardless of treatment arm assignment 30. Patients must not donate blood while participating in this study and for at least 90 days following the last dose of trial treatment