InDuRanS: A randomized phase II trial on induction immunochemotherapy followed by surgery or chemoradiotherapy and consolidation durvalumab in stage III NSCLC.

Abstract

TPS8125 Background: The optimal local treatment strategy for patients with resectable or borderline resectable stage IIIA/B (N2) non-small-cell lung cancer (NSCLC) remains controversial. Earlier randomized trials comparing surgery with definitive chemoradiotherapy (CRT) failed to demonstrate a survival advantage for either modality; however, these studies predated routine PET staging, modern radiotherapy techniques, and standard-of-care immunotherapy. Consolidation durvalumab after definitive CRT has significantly improved survival in unresectable stage III NSCLC, while neoadjuvant immunochemotherapy has shown promising pathologic and survival outcomes in resectable disease. Whether surgery or definitive CRT provides superior outcomes following induction immunochemotherapy in stage III NSCLC is unknown. The InDuRanS trial aims to address this question in a randomized setting. Methods: InDuRanS (ARO-2024-12; NCT06810609) is a prospective, multicenter, open-label, randomized phase II trial conducted across approximately 10 centers in Germany. Eligible patients have (borderline) resectable stage IIIA/B (N2) NSCLC without targetable EGFR or ALK alterations. All patients receive three cycles of induction immunochemotherapy consisting of durvalumab (1,500 mg every 3 weeks) combined with platinum-paclitaxel. Following PET-based restaging, patients with persistent resectable disease are randomized 1:1 to surgery (Arm A) or definitive CRT (Arm B). CRT consists of 60–70 Gy in conventional fractionation with two cycles of concurrent platinum-vinorelbine. Both treatment arms subsequently receive consolidation durvalumab (1,500 mg every 4 weeks) for up to 13 cycles. The primary endpoint is 2-year event-free survival (EFS). Secondary endpoints include overall survival, progression-free survival, treatment-related toxicity, surgical outcomes, and quality of life. Exploratory analyses include radiomics, plasma proteomics, circulating tumor DNA, and immune profiling. A total of 176 patients will be enrolled, with 158 evaluable patients planned for randomization. Interim safety analyses are scheduled after treatment completion in the first 10 randomized patients. The trial is currently open and recruiting.