A multi-arm phase II basket protocol testing reduced intensity immunotherapy across different cancers

1. WHO Performance Status 0 or 1. 2. Patients with locally advanced or metastatic cancer whose clinician has determined they are candidates for treatment with standard of care immune checkpoint inhibitor. 3. Patients aged > = 18years. 4. Adequate normal organ and marrow function. a. Haemoglobin > = 9.0g/dL (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 (This will not apply to subjects with confirmed Gilbert’s syndrome (i.e., persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of haemolysis or hepatic pathology), who will be allowed only in consultation with their physician). e. AST/ALT < = 3 x ULN. f. Calculated Creatinine Clearance level > 40mL/min by Cockcroft Gault formula (using actual body weight). 5. Resting 12-lead ECG on which QTcF must be < 450 ms. This will usually have been performed prior to commencement of the initial 12 weeks ICI. 6. Both men and women enrolled in this trial must be in agreement with trial policy on contraception during the treatment phase of the study. Egg donation, sperm donation and breastfeeding must be avoided. 7. Evidence of post-menopausal status or negative serum HCG pregnancy test for female pre-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). RENAL COHORT SPECIFIC INCLUSION CRITERIA: 1. Patients with un-resectable 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 3. Patient has received induction ipilumumab 1mg/kg (all four doses) and nivolumab 3mg/kg as first line treatment 4. Due to commence maintenance nivolumab with no evidence of progression (i.e. response or stable disease on cross sectional imaging on completion of initial 12 weeks treatment with ICI) MELANOMA COHORT SPECIFIC INCLUSION CRITERIA 1. Patients with locally advanced or metastatic melanoma 2. Patients have received single agent pembrolizumab first line for 3 months, with no evidence of progression (i.e. response or stable disease), and due to commence maintenance Pembrolizumab every 6 weeks; OR induction ipilumumab 1mg/kg and nivolumab 3mg/kg as first line treatment, and due to commence maintenance nivolumab with no evidence of progression (i.e. response or stable disease) on cross sectional imaging 12 weeks post initiation of ICI.

1. Patients who have received immune checkpoint inhibitors in a prior line of treatment 2. Patients whose planned treatment is the combination of anti-PD-1 and tyrosine kinase inhibitor eg, pembrolizumab-axitinib or the combination of traditional cytotoxic chemotherapy and anti-PD-1. 3. Patients with unresolved/untreated immune-related adverse events resulting from the first 3 months of treatment with standard of care immune checkpoint inhibitor 4. History of another previous malignancy, except for a) Malignancy treated with curative intent and with no known active disease > = 5 years before the first dose of IP and of low potential risk for recurrence. b) Adequately treated non-melanoma skin cancer without evidence of disease. c) Adequately treated carcinoma in situ without evidence of disease. d) Superficial bladder cancer 5. 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 (see co-enrolment section for further details). 6. Current or prior use of immunosuppressive medication within 14 days before starting immune checkpoint inhibitor, with the exceptions of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid. 7. Active infection including a. Tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and TB testing in line with local practice) b. Hepatitis B (known positive HBV surface antigen (HBsAg) result). Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody [anti-HBc] and absence of HBsAg) are eligible. c. Hepatitis C. Note: Patients positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA. d. Human immunodeficiency virus (positive HIV 1/2 antibodies). 8. Receipt of live attenuated vaccine within 30 days prior to the start of treatment. Note: Patients, if enrolled, should not receive live vaccine while receiving immune checkpoint inhibitor and up to 30 days after the last dose of immune checkpoint inhibitor. 9. Known allergy or 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. 13. Participants who have undergone any prior systemic anti-cancer treatment (previous participation in adjuvant studies allowed, providing the patient was on the observation/ placebo arm – this may require un-blinding of the patient) 14. Untreated brain metastases or brain metastases treated only with whole brain radiotherapy. (Patients are eligible if previous brain metastases treated with complete surgical resection, Stereotactic Brain Radiation Therapy (SBRT), or gamma knife with no subsequent evidence of progression and asymptomatic).