TROPION-Lung12: Phase 3 Trial of Datopotamab Deruxtecan in Early-Stage NSCLC Initiated
Key Insights
The TROPION-Lung12 phase 3 trial has begun, assessing adjuvant DATROWAY® (datopotamab deruxtecan) with or without rilvegostomig in resected stage 1 NSCLC patients.
The trial targets patients with ctDNA-positive status or high-risk pathological features, aiming to improve outcomes after surgery for early-stage non-small cell lung cancer (search).
DATROWAY®, a TROP2 (search)-directed antibody-drug conjugate, is being evaluated against standard of care to prevent disease recurrence in this high-risk population.
The first patient has been dosed in the TROPION-Lung12 phase 3 trial, evaluating the efficacy and safety of adjuvant DATROWAY® (datopotamab deruxtecan) plus rilvegostomig or rilvegostomig monotherapy versus standard of care in patients with stage 1 adenocarcinoma (search) non-small cell lung cancer (search) (NSCLC) after complete surgical resection who are ctDNA-positive or have other high risk pathological features. This trial, initiated by Daiichi Sankyo and AstraZeneca, seeks to address the unmet need for effective adjuvant therapies in early-stage NSCLC patients at high risk of relapse.
Addressing Recurrence Risk in Early-Stage NSCLC
Standard treatment for stage 1 NSCLC involves tumor resection, but recurrence rates can be as high as 40%. While adjuvant chemotherapy and/or immunotherapy may be offered to patients with stage 1b disease identified as high-risk, better strategies for identifying these patients and more effective treatment options are needed. The TROPION-Lung12 trial aims to fill this gap by evaluating DATROWAY® in combination with rilvegostomig, an immunotherapy, in patients identified through ctDNA screening or high-risk pathological features.
Trial Design and Endpoints
TROPION-Lung12 is a global, multicenter, three-arm, open-label phase 3 trial. Patients will be randomized in a 2:1:2 ratio to receive adjuvant DATROWAY® (6 mg/kg) in combination with rilvegostomig (750 mg), rilvegostomig (750 mg) monotherapy, or observation/standard of care adjuvant chemotherapy. The trial includes patients with stage 1 (stage 1a or 1b with tumors < 4 cm) adenocarcinoma (search) NSCLC who are ctDNA-positive or have high-risk pathological features.
The primary endpoint of TROPION-Lung12 is disease-free survival following complete tumor resection, assessed by blinded independent central review. Key secondary endpoints include patient-reported physical functions, patient-reported quality of life outcomes, overall survival, and safety. The trial plans to enroll approximately 660 patients across Asia, Europe, North America, and South America.
Investigational Therapies
DATROWAY® (datopotamab deruxtecan) is a TROP2 (search)-directed antibody-drug conjugate (ADC) discovered by Daiichi Sankyo and jointly developed and commercialized with AstraZeneca. It consists of a humanized anti-TROP2 IgG1 monoclonal antibody attached to a topoisomerase I inhibitor payload (DXd) via tetrapeptide-based cleavable linkers. Rilvegostomig is AstraZeneca’s PD-1/TIGIT bispecific antibody. The TIGIT component of rilvegostomig is derived from the clinical-stage anti-TIGIT antibody, COM902, developed by Compugen Ltd.
Expert Commentary
"After surgery for early-stage non-small cell lung cancer (search), there is no established consensus on adjuvant therapy. As a result, patients may either undergo observation or receive adjuvant chemotherapy and/or immunotherapy if they have stage 1b disease and are determined to be at high risk for disease recurrence," said Mark Rutstein, MD, Global Head, Oncology Clinical Development, Daiichi Sankyo. "The TROPION-Lung12 trial will help us better understand the role of DATROWAY in combination with immunotherapy in the adjuvant setting as a potential treatment regimen to help prevent disease recurrence in patients with high risk stage 1 adenocarcinoma (search) following surgery."
Cristian Massacesi, MD, Chief Medical Officer and Oncology Chief Development Officer, AstraZeneca, added, "With TROPION-Lung12, we are simultaneously deploying a novel strategy for identifying patients with lung cancer who are at an increased risk of disease recurrence after surgery and evaluating novel treatment options in the adjuvant setting, including rilvegostomig with and without DATROWAY. The ambitious approach in this trial underscores our commitment to both enabling more personalized treatment decisions and delivering innovative treatment options to patients with cancer."