INCLUSION CRITERIA

        Participants are eligible to be included in the study only if all of the following criteria
        apply:

          1. Histological confirmation of RCC of predominantly (>50%) clear cell type.

          2. Presence of metastatic / locally advanced inoperable disease.

          3. Current evidence of disease progression on immuno-oncology (IO) therapy as determined
             by CT / MRI imaging performed within 28 days prior to the first dose of study drug.
             Last dose of IO therapy must have been administered within 42 days prior to the first
             dose of study drug. IO therapy may consist of either:

               1. First-line Ipilimumab / Nivolumab combination OR

               2. Second / Third-line single agent Nivolumab OR

               3. Other PD-1 / PD-L1 / anti-CTLA-4 therapy within a clinical trial

          4. Measurable disease according to RECIST version 1.1 criteria.

          5. Site(s) of disease which are easily accessible and suitable for repeated biopsies
             (bone metastases are not suitable as a biopsy site).

          6. Provision of archival tumour tissue sample (formalin-fixed paraffin embedded (FFPE)
             tissue blocks) and a newly obtained core or excisional biopsy of a tumour lesion not
             previously irradiated.

          7. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
             Evaluation of ECOG is to be performed within 7 days prior to the first dose of study
             drug.

          8. Age > 18 years.

          9. Have adequate organ function as defined below. Specimens must be collected within 14
             days prior to the start of study treatment.

               1. Absolute neutrophil count (ANC) ≥1.5 x109/L

               2. Platelets ≥100 x109/L

               3. Haemoglobin ≥9.0 g/dL or ≥5.6 mmol/L

               4. Creatinine ≤1.5 × Upper Limit of Normal (ULN) OR Measured or calculated
                  creatinine clearance (CrCl) ≥30 mL/min for participant with creatinine levels OR
                  (Glomerular Filtration Rate (GFR) can also be used in place of creatinine or CrCl
                  >1.5 × institutional ULN

               5. Total bilirubin ≤1.5 ×ULN OR direct bilirubin ≤ULN for participants with total
                  bilirubin levels >1.5 × ULN

               6. Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) ≤2.5 × ULN
                  (≤5 × ULN for participants with liver metastases)

               7. International normalised ratio (INR) OR prothrombin time (PT) / Activated partial
                  thromboplastin time (aPTT) ≤1.5 × ULN unless participant is receiving
                  anticoagulant therapy as long as PT or aPTT is within therapeutic range of
                  intended use of anticoagulants

         10. Able to take oral medications.

         11. Life expectancy of > 6 months in the opinion of the investigator.

         12. Male participants must agree to use a form of contraception as detailed in Appendix 3
             of this protocol during the treatment period and for at least 180 days after the last
             dose of study treatment and refrain from donating sperm during this period.

         13. Female participants are eligible to participate if they are not pregnant (see Appendix
             3), not breastfeeding, and at least one of the following conditions applies:

               1. Not a woman of childbearing potential (WOCBP) as defined in Appendix 3 OR

               2. A WOCBP who agrees to follow the contraceptive guidance in Appendix 3 during the
                  treatment period and for at least 180 days after the last dose of study
                  treatment.

         14. The participant provides written informed consent for the trial including consent to
             all samples.

        EXCLUSION CRITERIA

        Participants are excluded from the study if any of the following criteria apply:

          1. Treatment with more than one prior line of IO therapy (including previous standard of
             care and trial treatments).

          2. High burden / symptomatic disease which in the opinion of the treating investigator
             requires Tyrosine Kinase Inhibitors (TKI) / alternative therapeutic approach.

          3. Prior treatment with either pembrolizumab or cyclophosphamide.

          4. Known severe hypersensitivity (≥Grade 3) to pembrolizumab, cyclophosphamide and/or any
             of their excipients.

          5. Prior intolerance to IO therapy (any > Grade 2 toxicity which required permanent IO
             treatment discontinuation).

          6. Ongoing Adverse Events (AEs) due to previous therapies or surgery which have not
             resolved to ≤ Grade 1 or baseline. Participants with ≤ Grade 2 neuropathy may be
             eligible.

          7. Active autoimmune disease that has required systemic treatment in the past 2 years
             (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive
             drugs). Replacement therapy (e.g. levothyroxine, insulin, or physiologic
             corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is
             not considered a form of systemic treatment.

          8. Diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in
             dosing exceeding 10 mg daily of prednisolone equivalent) or any other form of
             immunosuppressive therapy within 7 days prior to the first dose of study drug.

          9. Known additional malignancy that is progressing or has required active treatment
             within the past 3 years. Note: Participants with basal cell carcinoma of the skin,
             squamous cell carcinoma of the skin, superficial transitional cell carcinoma of the
             bladder / urothelial tract, or carcinoma in situ (e.g. breast carcinoma, cervical
             cancer in situ) that have undergone potentially curative therapy are not excluded.

         10. Prior radiotherapy within 2 weeks of start of study treatment. Participants must have
             recovered from all radiation-related toxicities, not require corticosteroids, and not
             have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation
             (≤2 weeks of radiotherapy) to non-CNS (Central Nervous System) disease.

         11. Live vaccine within 30 days prior to the first dose of study drug. Examples of live
             vaccines include, but are not limited to, the following: measles, mumps, rubella,
             varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG),
             and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed
             virus vaccines and are allowed; however, intranasal influenza vaccines (e.g. FluMist®)
             are live attenuated vaccines and are not allowed.

         12. Currently participating in or has participated in a study of an investigational agent
             or has used an investigational device within 4 weeks prior to the first dose of study
             treatment. Note: Participants who have entered the follow-up phase of an
             investigational study may participate as long as it has been 4 weeks after the last
             dose of the previous investigational agent.

         13. Known previous or current Central Nervous System (CNS) metastases and/or carcinomatous
             meningitis. Note: no testing is required.

         14. History of (non-infectious) pneumonitis that required steroids or has current
             pneumonitis.

         15. Active infection requiring systemic therapy or has had requirement for antibiotics
             within 14 days prior to first dose of study treatment.

         16. Known history of Human Immunodeficiency Virus (HIV). Note: no testing for HIV is
             required.

         17. Known history of Hepatitis B (defined as Hepatitis B surface antigen (HBsAg) reactive)
             or known active Hepatitis C virus (defined as HCV RNA positive) infection. Note: no
             testing for Hepatitis B and Hepatitis C is required.

         18. Known history of active tuberculosis (Bacillus Tuberculosis, TB). Note: no testing for
             TB is required.

         19. History or current evidence of any condition, therapy, or laboratory abnormality that
             might confound the results of the study, interfere with the subject's participation
             for the full duration of the study, or is not in the best interest of the subject to
             participate, in the opinion of the treating investigator.

         20. Known psychiatric or substance abuse disorders that would interfere with cooperation
             with the requirements of the trial.

         21. Pregnant or breastfeeding, or expecting to conceive or father children within the
             projected duration of the study, starting with the screening visit through 180 days
             after the last dose of trial treatment. Note: WOCBP must have a negative urine
             pregnancy test within 72 hours prior to trial entry (see Appendix 3). If the urine
             test is positive or cannot be confirmed as negative, a serum pregnancy test will be
             required. In the event that 72 hours have elapsed between the screening pregnancy test
             and the first dose of study treatment, another pregnancy test (urine or serum) must be
             performed and must be negative in order for subject to start receiving study
             medication.