Background: Concurrent chemoradiation therapy (CRT) followed by durvalumab consolidation therapy has demonstrated significant survival benefit for unresectable stage III non-small cell lung cancer (NSCLC) in PACIFIC trial. However, there are still 20%-30% patients who have disease progression (PD) or intolerable toxicity. This prospective study aimed to evaluate safety and clinical activity of concurrent durvalumab plus CRT followed by durvalumab in unresectable stage III NSCLC (NCT04982549). Methods: This is a single-arm, open-label, multicenter phase II clinical trial and planned to enroll 35 patients with unresectable stage III NSCLC of any PD-L1 expression level and Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. All of patients will receive concurrent durvalumab 1500mg every 4 weeks plus SoC CRT followed by durvalumab monotherapy 1500mg every 4 weeks until PD or unacceptable toxicity. One cycle of induction durvalumab plus chemotherapy is allowed before radiotherapy upon investigator discretion. The primary endpoint is the incidence of grade ≥3 immune-mediated adverse event (AE). Here we report the preliminary clinical activity and safety of a preplanned interim analysis of this study. Results: By September 2022, 28 patients finished concurrent durvalumab plus CRT treatment and were included for analysis. 21 (75%) of 28 patients had radiographic tumor evaluation and entered the consolidation treatment stage, 7 (25%) patients discontinued treatment without radiographic tumor evaluation because of intolerable AE (5 patients) or withdrawing from the study (2 patients). 20 (71.4%) of 28 patients received one cycle induction therapy of durvalumab plus chemotherapy. The median age of these 28 patients was 64 years old, 26 (92.9%) of 28 patients with ECOG performance status of 1, and 14 (50%) of 28 patients were squamous carcinoma. Disease stage was IIIA (42.9%, 12/28), IIIB (39.3%, 11/28) and IIIC (17.9%, 5/28), with most of them (89.3%, 25/28) had N2/N3 lymphatic metastasis. 19 (90.5%) of 21 patients achieved objective response. Median interval from enrollment to the first radiological evaluation was 112 days. Grade ≥3 treatment-related adverse event (TRAEs) occurred in 13(46.4%) of 28 patients, including six (21.4%) possibly related to durvalumab. Conclusions: The interim results from CRUISER study showed promising clinical activity and manageable toxicity of durvalumab plus concurrent CRT followed by durvalumab for unresectable stage III NSCLC. The survival outcome and biomarker exploration will be analyzed upon data maturity. Phase 3 PACIFIC-2 study investigating clinical outcome of concurrent durvalumab plus CRT in unresectable NSCLC is ongoing. Clinical trial information: NCT04982549.