The increased benefit of ICI for patients with double-mutated tumours observed in the study cohort was confirmed in the two external validation cohorts, HD-ICI: HR = 0.71 (0.55–0.92), SU2C-ICI: HR = 0.54 (0.28–1.03), and MSK-ICI: HR = 0.35 (0.14–0.88) in the analysis of OS and similar results were observed in the analysis of PFS. Here, SIK1 is linked to neoplasm.