TROPION-Lung12: A phase 3 study of adjuvant datopotamab deruxtecan and rilvegostomig in ctDNA-positive or high-risk pathology stage I NSCLC.

Abstract

Objective: Five-year disease recurrence rates for patients with stage I non-small cell lung cancer (NSCLC) post-surgery are variable (15%-40%). There is an urgent need for novel biomarker strategies to identify high-risk patients who may benefit from adjuvant treatment. High-risk pathological features, including high-grade histology and lymphovascular or visceral pleural invasion, serve as independent risk factors for worse outcomes. Pre-operative circulating tumor DNA (ctDNA) detection is also correlated with poorer outcomes in stage I NSCLC. Datopotamab deruxtecan (Dato-DXd), an antibody-drug conjugate composed of a humanized anti-TROP2 antibody conjugated to a potent topoisomerase I inhibitor via a plasma-stable linker, and rilvegostomig, an Fc-reduced, monovalent, bispecific, humanized IgG1 antibody targeting both PD-1 and TIGIT receptors, have shown promise in NSCLC studies. Combining Dato-DXd with rilvegostomig may improve treatment outcomes in select patients with stage I NSCLC.

Methods: TROPION-Lung12 (NCT06564844) is a phase 3, randomized study enrolling approximately 660 patients with stage I adenocarcinoma without actionable genomic alterations who have undergone complete surgical resection. Eligible patients must have pre-operative ctDNA-positive status or ≥1 high-risk pathological feature(s). Patients will be randomized 2:1:2 to receive Dato-DXd (6 mg/kg IV Q3W) plus rilvegostomig (750 mg IV Q3W) for 4 cycles followed by rilvegostomig (up to 12 months/18 cycles total); rilvegostomig alone (up to 12 months/18 cycles total); or standard of care (SoC) for up to 12 months. The primary endpoint is disease-free survival assessed using blinded independent central review per RECIST v1.1, with key secondary endpoints including overall survival, for Dato-DXd plus rilvegostomig vs SoC arms.