Initial results from the TROPION-Lung04 Phase Ib trial showed that datopotamab deruxtecan (Dato-DXd) in combination with Imfinzi (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 (NSCLC) without actionable genomic alterations.
These data were presented today in a late-breaking oral presentation (#OA05.06) at the International Association for the Study of Lung Cancer (IASLC) 2023 World Conference on Lung Cancer (WCLC).
Datopotamab deruxtecan is a specifically engineered TROP2-directed DXd antibody drug conjugate (ADC) being jointly developed by AstraZeneca and Daiichi Sankyo.
More than one million people worldwide are diagnosed with advanced NSCLC each year.1,2 While 1st-line treatment with immune checkpoint inhibitors with or without chemotherapy has improved outcomes for patients with NSCLC without actionable genomic alterations, like EGFR or ALK, most patients eventually experience disease progression.3-5 TROP2 is a protein broadly expressed in a large majority of NSCLC tumours.6 There are currently no TROP2-directed ADCs approved for the treatment of patients with lung cancer.7,8
In previously untreated patients, datopotamab deruxtecan plus durvalumab (doublet; n=14) demonstrated an objective response rate (ORR) of 50.0%, including 7 partial responses (PR), and a disease control rate (DCR) of 92.9%. Response rates were higher in patients receiving datopotamab deruxtecan plus durvalumab and carboplatin (triplet; n=13) which demonstrated an ORR of 76.9%, including 10 PRs, and a DCR of 92.3%. Responses were observed across PD-L1 expression levels.
Saiama Waqar, MD, Siteman Cancer Center, Washington University School of Medicine, St. Louis, Missouri, and investigator in the trial, said: “Most patients with advanced non-small cell lung cancer experience disease progression after initial treatment, underscoring the need for more effective first-line treatment options. The TROPION-Lung04 results offer preliminary evidence for the efficacy of datopotamab deruxtecan in combination with durvalumab and chemotherapy in first-line advanced non-small cell lung cancer with no new safety signals. We eagerly await enrolment and results from the Phase III programme evaluating various datopotamab deruxtecan and immune checkpoint inhibitor combinations in this setting.”
Cristian Massacesi, Chief Medical Officer and Oncology Chief Development Officer, AstraZeneca, said: “Following the positive high-level results of TROPION-Lung01, these initial TROPION-Lung04 results in the first-line setting reinforce our confidence in datopotamab deruxtecan as a potential treatment option for patients with advanced non-small cell lung cancer. Through our robust clinical programme we are eager to continue evaluating this TROP2-directed antibody drug conjugate in lung cancer across treatment settings, alone and in novel combinations.”
Mark Rutstein, MD, Global Head, Oncology Clinical Development, Daiichi Sankyo, said: “These early trial results further demonstrate the potential for datopotamab deruxtecan to enhance response to immune checkpoint inhibitors in patients with advanced non-small cell lung cancer and without actionable genomic alterations. We look forward to continuing to evaluate this promising TROP2-directed antibody drug conjugate in multiple ongoing Phase III trials to address what has long been an unmet need for the lung cancer community across treatment settings.”
In both previously treated and untreated patients, the safety profiles of datopotamab deruxtecan and Imfinzi 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 (TEAEs) 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 (occurring in more than 15% of patients) were anaemia (36%) and thrombocytopenia (21%). No Grade 3 or greater TEAE occurred in more than 15% of patients receiving doublet therapy. Across treatment cohorts, there were four interstitial lung disease (ILD) 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.
Summary of TROPION-Lung04 Efficacy Results
