Background: In the PACIFIC study, progression-free survival (PFS) and overall survival (OS) of patients with unresectable, locally advanced, stage III non-small cell lung cancer (NSCLC) were prolonged by durvalumab as maintenance therapy after radical concurrent chemoradiotherapy using platinum-based antitumor agents. However, no data were obtained to reveal the efficacy of durvalumab after radiation monotherapy in patients unsuitable for chemoradiotherapy. Here, we describe an ongoing single-arm, prospective, open-label, multicenter phase II trial of durvalumab in patients with NSCLC ineligible for stage III chemoradiotherapy following radiation monotherapy (SPIRAL-RT study). Methods: Durvalumab at 10 mg/kg body weight is administered every 2 weeks after radiation therapy until individual patients meet the discontinuation criteria. The treatment duration is up to 12 months. The primary endpoint is the 1-year PFS rate. Secondary endpoints are response rate, PFS, OS, and safety. Durvalumab treatment after radiation monotherapy is expected to prolong 1-year PFS rate and have acceptable adverse events. Discussion: We are conducting an intervention study to investigate the safety and efficacy of durvalumab treatment in patients with NSCLC ineligible for stage III chemoradiotherapy following radiation monotherapy.