Pembrolizumab in Intermediate Risk Recurrent Non-muscle Invasive Bladder Cancer (NMIBC)

Inclusion Criteria: In order to be eligible for participation in this trial, the subject must: 1. Be willing and able to provide written informed consent for the trial and comply with the protocol scheduled follow-up visits and examinations for the duration of the study. 2. Be ≥ 18 years of age on day of signing informed consent. 3. Have recurrent NMIBC for which adjuvant treatment post TURBT would be a reasonable treatment option. 4. Main study only: a. Have recurrent, multiple (minimum 2) tumours consistent with NMIBC. b. Have at least one lesion of between 5-10mm in size clinically that can be left un-resected at TURBT as the marker lesion. c. Have histologically confirmed low grade transitional cell NMIBC at original and any subsequent diagnosis. 5. Have a normal upper urinary tract (as evidenced by ultrasound or CT urography within 2 years prior to randomisation) and no evidence of tumour in prostatic urethra at flexible cystoscopy. 6. Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale. 7. Have adequate organ function as defined below: Haemoglobin (Hb) ≥ 9 g/dL without transfusion or erythropoietin (EPO) dependency Absolute neutrophil count (ANC) ≥ 1.5 x 109/L Platelet count ≥ 100 x 109/L Total bilirubin ≤ 1.5 times the upper limit of normal (ULN) or direct bilirubin \< ULN for subjects with total bilirubin levels \> 1.5 x ULN Serum alanine aminotransferase (ALT) and/or serum aspartate aminotransferase (AST) ≤ 2.5 x ULN Serum creatinine OR Measured or calculated creatinine clearance ≤ 1.5 x ULN OR ≥ 60ml/min for subject with creatinine levels \> 1.5 x institutional ULN Albumin ≥ 25g/L International Normalized Ratio (INR) or Prothrombin Time (PT) and Activated Partial Thromboplastin Time (aPTT) ≤ 1.5 x ULN unless subject is receiving anticoagulant therapy as long as PT or APTT is within therapeutic range of intended use of anticoagulants a Creatinine clearance should be calculated as per institutional standard 8. Female subjects of childbearing potential should have a negative urine or serum pregnancy test within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. 9. Both male and female subjects of childbearing potential must be willing to use an adequate method of contraception as outlined in section 5.1 for the course of the study and until 120 days after the last dose of the study medication. Exclusion Criteria: The subject must be excluded from participating in the trial if the subject: 1. Has received prior radiotherapy to the pelvis. 2. Has significant urinary incontinence or known bladder instability. 3. Main study only: 1. Has more than 2 out of 3 of the following present at the current time: i. ≥8 tumours ii. Tumour ≥3cm in size iii. Frequent recurrence (\>1/year) 2. Has a previous history of any of the following: T1 tumour, high grade/G3 tumour, carcinoma in situ, multiple recurrent large (\>3cm) Ta, G1 or G2 tumours. 3. Had a primary tumour of unknown pathological stage or grade. 4. Has disease for which resection of all visible tumours is not possible. 4. Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 28 days of the first dose of trial treatment. 5. Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment. Subjects requiring use of inhaled or intranasal corticosteroids or local steroid injections would not be excluded. 6. Has a known history of active tuberculosis (TB). 7. Has received intravesical Bacillus Calmette-Guerin (BCG) treatment within 30 days prior to the first dose of trial treatment. 8. Has hypersensitivity to pembrolizumab or any of its excipients. 9. Has had treatment with any other anti-cancer monoclonal antibody within 28 days prior to enrolment or who has not recovered (i.e. ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier. 10. Has had treatment with prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks of administration of study drug or who has not recovered (i.e. ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent. 11. Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer. 12. Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurological symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for a t least 7 days prior to trial treatment. This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability. 13. Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents or immunosuppressive drugs). Replacement therapy (e.g. thyroxine, insulin or physiologic corticosteroids replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment. 14. Has a known history of, or any evidence of active, non-infectious pneumonitis. 15. Has an active or intractable infection requiring systemic therapy. 16. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating Investigator. 17. Has a known psychiatric or substance abuse disorder that would interfere with cooperation with the requirements of the trial. 18. Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through to 120 days after the last dose of trial treatment. 19. Has received prior therapy with an anti-programmed cell death protein 1 (anti-PD-1), anti-programmed death ligand 1 (anti PD-L1), or anti-programmed death ligand 2 (anti-PD-L2) agent. 20. Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies). 21. Has known active Hepatitis B (e.g. HBsAg reactive) or Hepatitis C (e.g. hepatitis C virus \[HCV\] RNA \[qualitative\] is detected). 22. Has received a live vaccine within 30 days prior to the first dose of trial treatment.