Phase i trials in melanoma: A framework to translate preclinical findings to the clinic

•We present a mathematical model driven framework for virtual clinical trials (phase i trials).•The phase i trial paradigm: model development, cohort generation, stratification, and optimizing treatment schedules.•Phase i trial in melanoma captured the observed heterogeneity of patient responses to treatment.•Phase i trial stratified cohort predicts main differentiators of patient survival.•Model predicted optimal treatment schedule not only improved survival but also decreased toxicity.