Daiichi Sankyo, AstraZeneca present initial results from TROPION-Lung04 phase 1b

Initial results from the TROPION-Lung04 phase 1b trial showed that datopotamab deruxtecan in combination with durvalumab, an anti-PD-L1 therapy, with or without carboplatin demonstrated encouraging responses and no new safety signals in patients with previously untreated advanced or metastatic non-small cell lung cancer without actionable genomic alterations. These data were presented during a late-breaking oral presentation at the IASLC 2023 World Conference on Lung Cancer hosted by the International Association for the Study of Lung Cancer. Datopotamab deruxtecan is a specifically engineered TROP2 directed DXd antibody drug conjugate being jointly developed by Daiichi Sankyo and AstraZeneca. In previously untreated patients, datopotamab deruxtecan plus durvalumab demonstrated an objective response rate of 50.0%, including seven partial responses and a disease control rate of 92.9%. Response rates were higher in patients receiving datopotamab deruxtecan plus durvalumab and carboplatin which demonstrated an ORR of 76.9%, including 10 PRs and a DCR of 92.3%. Responses were observed across PD-L1 expression levels. In both previously treated and untreated patients, the safety profiles of datopotamab deruxtecan and durvalumab with and without carboplatin were consistent with other clinical trials and with the known safety profile of each agent. Grade 3 or greater treatment-emergent adverse events occurred in 42.1% of patients receiving doublet therapy and 71.4% of patients receiving triplet therapy. In patients receiving triplet therapy, the most common grade 3 or greater TEAEs were anemia and thrombocytopenia. No grade 3 or higher TEAE occurred in more than 15% of patients receiving doublet therapy. Across treatment cohorts, there were four interstitial lung disease events adjudicated as drug-related by an independent committee including one grade 1 event, two grade 2 events and one grade 4 event. No grade 5 ILD events were observed. In the doublet cohort, 73.7% of patients were previously untreated. In the triplet cohort, 92.9% of patients were previously untreated. Both the doublet and triplet cohorts included patients with PD-L1 expression levels ranging from less than 1%, 1% to 49% and 50% or greater, respectively. As of the March 6, 2023 data cut-off, median study duration was six months for both cohorts and treatment was ongoing in 31.6% and 50.0% of patients in the doublet and triplet cohorts, respectively.