In conclusion, the combination of palliative RT for bone metastasis with nivolumab was safe and showed modest anti-tumor activity in cohort A, but not in cohort B. Further investigations regarding the optimal dose and schedule of the combination of RT and ICB, the optimal RT treatment site, the addition of other molecular targeted therapies such as PARP inhibitors or CDK4/6 inhibitors, or novel biomarkers to identify the best candidate for this treatment strategy are warranted. Here, CDK4 is linked to bone metastasis.