GENERAL INCLUSION CRITERIA

1.  Patients with locally advanced or metastatic cancers for which immune checkpoint inhibitors are standards-of-care and whose clinician has determined they are candidates for treatment with this approach (see also Cohort Specific Inclusion Criteria, below).

2. WHO Performance Status 0 or 1.

3. Patients aged ≥18years.

4. Adequate normal organ and marrow function:

   a. Haemoglobin ≥90g/L (transfusions will be allowed within 2 weeks prior to randomisation in order to achieve the entry criteria).

   b. Absolute neutrophil count (ANC) ≥1.5 x 109/L (≥1500 per mm3).

   c. Platelet count ≥100 x 109/L (≥100,000 per mm3).

   d. Bilirubin ≤1.5 x ULN or patients with confirmed Gilbert’s syndrome (i.e. persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of haemolysis or hepatic pathology).

   e. AST/ALT ≤3 x ULN. f. eGFR ≥40mL/min by CKD-EPI formula.

5. Both men and women enrolled in this trial must be in agreement with trial policy on contraception (see Section 5.8) during the treatment phase of the study. Egg donation, sperm donation and breastfeeding must be avoided.           

6. Evidence of post-menopausal status or negative serum HCG pregnancy test for female pre/peri-menopausal patients. Women will be considered post-menopausal if they have been amenorrhoeic for 12 months without an alternative medical cause. The following age-specific requirements apply:

a. Women <50 years of age will be considered post-menopausal if they have been amenorrhoeic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinising hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution or underwent surgical sterilisation (bilateral oophorectomy or hysterectomy).
b. Women ≥50 years of age will be considered post-menopausal if they have been amenorrhoeic for 12 months or more following cessation of all exogenous hormonal treatments, had radiation-induced menopause with last menses >1 year ago, had chemotherapy-induced menopause with last menses >1 year ago, or underwent surgical sterilisation (bilateral oophorectomy, bilateral salpingectomy, or hysterectomy).

COHORT SPECIFIC INCLUSION CRITERIA

In addition to the general inclusion criteria, the following cohort-specific eligibility criteria apply.

Renal cohort specific inclusion criteria: 

1. Patients with unresectable locally advanced or metastatic renal cell carcinoma (including clear cell and papillary histologies).

2. Intermediate or poor risk as defined in the International Metastatic Renal Cell Carcinoma Database Consortium criteria (prior to the initial induction treatment with ICI combination).

3. Patients have received at least one dose of induction ipilumumab and nivolumab.

4. No evidence of progression on ipilimumab and nivolumab induction therapy and due to commence maintenance nivolumab (i.e. response or stable disease on cross sectional imaging on completion of induction treatment with ICI combination).

Melanoma cohort specific inclusion criteria:

1. Patients with locally advanced (unresectable) or metastatic melanoma, including primary mucosal but not uveal melanoma.

2. No evidence of progression on ipilimumab and nivolumab induction therapy, have received at least one dose of induction ipilimumab and are due to commence maintenance nivolumab (i.e. response or stable disease on cross sectional imaging - including where present any brain metastases - on completion of induction treatment with ICI combination).
   Or
   Patients have received single agent pembrolizumab first line, with no evidence of progression (i.e. response or stable disease - including where present any brain metastases) on first response assessment, and due to continue pembrolizumab every 6 weeks.

PATIENT EXCLUSION CRITERIA 

1.  Patients who have received ICI in a prior line of treatment.

2. Patients who have undergone any prior systemic anti-cancer treatment except for patients with melanoma who have received BRAF/MEK inhibition which is allowed.

3. Patients where treatment is the combination of anti-PD-1 and tyrosine kinase inhibitor (e.g. pembrolizumab+axitinib) or the combination of traditional cytotoxic chemotherapy and anti-PD-1.

4. History of another previous malignancy, except for:

   a. Malignancy treated with curative intent and with no known active disease ≥5 years prior to the first dose of ICI.

   b. Adequately treated non-melanoma skin cancer without evidence of current, active disease.

   c. Adequately treated carcinoma in situ without evidence of current, active disease.

   d. Non-muscle invasive bladder cancer.

5. Concurrent enrolment in another interventional clinical study, unless in the follow-up period, except where approved by the CTU (see co-enrolment section for further details).

6. Current or prior use of immunosuppressive medication within 7 days of starting trial treatment, with the exceptions of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10mg/day of prednisone, or an equivalent corticosteroid.

7. Active infection that would preclude treatment with immune checkpoint inhibitors (e.g. Tuberculosis).

8. Receipt of a live attenuated vaccine within 30 days prior to the start of treatment. Note: Patients, if enrolled, should not receive a live vaccine while receiving immune checkpoint inhibitor and up to 30 days after the last dose of immune checkpoint inhibitor.

9. Known allergy or unmanageable hypersensitivity to immune checkpoint inhibitor.

10. Pregnant or breastfeeding patients.

11. Uncontrolled adrenal insufficiency.

12. Any serious or uncontrolled medical or psychiatric disorder that, in the opinion of the investigator, may increase the risk associated with study participation or study drug administration, impair the ability of the subject to receive protocol therapy, interfere with participation and/or compliance in the trial, or interfere with the interpretation of study results.