MELCHRONO: A Prospective Randomized Study Investigating Chrono-immunotherapy for Advanced Melanoma.

Inclusion Criteria: * Written informed consent according to Swiss law and ICH GCP E6 regulations before registration and prior to any trial specific procedures. * Histologically confirmed unresectable cutaneous stage III or stage IV melanoma. Note: Participants with central nervous system (CNS) metastases are eligible. * Participants with a previously treated other malignancy are eligible, if the risk of the prior malignancy interfering with either safety or efficacy endpoints is very low. * Measurable or evaluable disease. * Age ≥ 18 years. * Patients deemed suitable for ICI therapy based on the local investigator's clinical assessment. * ECOG performance status 0-2. * Women of childbearing potential must use effective contraception , not be pregnant or lactating and agree not to become pregnant during trial treatment and until 5 months after the last dose of trial treatment. A negative pregnancy test before inclusion into the trial is required for all women of childbearing potential. * Men agree not to donate sperm or to father a child during trial treatment and until 5 months after the last dose of trial treatment. Exclusion Criteria: * Prior treatment with any systemic anti-cancer therapy; with the exception of prior adjuvant anti-PD-1 or BRAF/MEK inhibitor therapy if the time from last dose to recurrence is more than 6 months. * Recent treatment (within 28 days prior to first dose) with any experimental drug. * Known history of allogeneic organ transplant. * Uveal or …