We present the preclinical rationale and clinical data from a phase 1b trial investigating the STING agonist dazostinag plus pembrolizumab following hypofractionated radiotherapy (RT) in patients with advanced non–small cell lung cancer (NSCLC), triple-negative breast cancer (TNBC), or squamous cell carcinoma of the head and neck (SCCHN) whose disease had progressed on prior checkpoint inhibitors (CPI; NCT04879849). The gene discussed is STING1; the disease is head and neck squamous cell carcinoma.