A Phase I clinical study published in Clinical Cancer Research showed Personalis’ NeXT Personal minimal residual disease (MRD) whole‑genome sequencing assay predicted immunotherapy response across multiple metastatic solid tumors. Investigators tracked circulating tumor DNA (ctDNA) longitudinally and found early ctDNA declines correlated with improved progression‑free and overall survival. The multicohort analysis included retrospective and prospective cohorts, with ctDNA reductions of ~30% before the second treatment cycle linked to better outcomes. ctDNA clearance was associated with a threefold increase in median PFS, and sustained MRD negativity predicted durable survival. If validated prospectively, tumor‑informed MRD monitoring could guide early treatment decisions, distinguish true progression from pseudoprogression, and streamline biomarker‑driven trial designs. Clinical adoption will hinge on standardized timing, sensitivity across tumor types, and integration into care pathways.