Treatment schedule and assessments
toxicity, tumour, melanoma, mismatch repair-deficient Colorectal Cancer
DISEASE PROGRESSION, TUMOUR, MELANOMA
Participants in Arm A will receive SOC interval ICI (480 mg nivo-lumab 4 weekly after ipilimumab and nivolumab regimens) commencing 6 weeks after their last infusion prior to randomisation.Participants in Arm B will receive extended interval ICI, which in stage I is doubling the dosing interval of Arm A (SOC interval):Additional tumour cohorts will mirror the renal cohort if treated with ipilimumab/nivolumab combinations (e.g. patients with melanoma) randomised at the point they proceed to nivolumab monotherapy. If treated with pembrolizumab (e.g. melanoma or mismatch repair-deficient Colorectal Cancer) with a SOC of 400 mg pem-brolizumab 6 weekly, the experimental arm for stage I will be 12 weekly administration.Treatment will be given as part of the trial until disease progression, toxicity that precludes further treatment, participant preference or for 1 year 9 months from the start of randomised treatment (i.e. 2 years total treatment). Participants who are still responding to ICI treatment at 2 years will have the option to continue treatment off trial if part of their normal care. Participants experiencing progression on the extended dosing interval (Arm B) will be offered treatment intensification (i.e. reverting to SOC ICI dosing frequency, as per Arm A) at the participants and clinician's discretion.The trial assessment schedule for each cohort is aligned with standard practice. Participants will be clinically assessed at baseline and every 4 weeks for the trial duration regardless of treatment status or progression. Since the COVID-19 pandemic clinical assessments are often conducted remotely, and the REFINE assessment schedule supports this, if possible, to collect all necessary clinical information and this is deemed appropriate by the investigator.Participants in both arms have a CT with contrast of the chest, abdomen and pelvis (or Positron Emission Tomography (PET)-CT +/− brain surveillance if appropriate in the melanoma cohort) carried out at baseline and then every 12 weeks until disease progression or treatment discontinuation, whichever occurs later.