The first patients have been dosed in three global phase 3 trials assessing datopotamab deruxtecan (Dato-DXd)-based therapies for locally advanced or metastatic nonsquamous non-small cell lung cancer (NSCLC). Datopotamab deruxtecan, a TROP2-directed DXd antibody drug conjugate (ADC) discovered by Daiichi Sankyo, is co-developed with AstraZeneca.
The TROPION-Lung10 trial examines datopotamab deruxtecan combined with rilvegostomig—AstraZeneca’s PD-1/TIGIT bispecific antibody—or rilvegostomig alone, versus pembrolizumab in patients with high PD-L1 expression (≥50%) without actionable mutations. TROPION-Lung14 evaluates the combination of datopotamab deruxtecan and osimertinib, AstraZeneca's EGFR tyrosine kinase inhibitor, against osimertinib alone in untreated, EGFR-mutated nonsquamous NSCLC. TROPION-Lung15 assesses datopotamab deruxtecan, with or without osimertinib, compared to platinum-based chemotherapy in patients with advanced EGFR-mutated NSCLC that progressed after osimertinib.
“These trials are essential to understanding datopotamab deruxtecan’s potential in treating different lines and types of lung cancer,” said Mark Rutstein, MD, Global Head, Oncology Clinical Development at Daiichi Sankyo. “Our expanding TROPION program underscores our commitment to lung cancer research.”
AstraZeneca’s Chief Medical Officer, Cristian Massacesi, MD, added, “Combining an ADC with targeted or bispecific immunotherapies may produce more durable tumor responses. These phase 3 trials reflect our pursuit of innovative combination therapies within our oncology pipeline and for TROP2-directed ADCs across NSCLC settings.”