Datopotamab deruxtecan plus Imfinzi showed promising clinical activity in the first-line advanced non-small cell lung cancer setting in TROPION-Lung04 Phase Ib trial
AstraZeneca and Daiichi Sankyo’s datopotamab deruxtecan plus Imfinzi with or without chemotherapy demonstrated objective response rates of 77% and 50% and disease control rates of 92% and 93%, respectively.
Datopotamab deruxtecan is a specifically engineered TROP2-directed DXd antibody drug conjugate (ADC) being jointly developed by AstraZeneca and Daiichi Sankyo. Datopotamab deruxtecan is comprised of a humanized anti-TROP2 IgG1 monoclonal antibody, developed in collaboration with Sapporo Medical University, attached to a number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers.
A comprehensive development programme is underway globally with more than 12 trials evaluating the efficacy and safety of datopotamab deruxtecan across multiple TROP2-targetable tumours, including NSCLC, triple-negative breast cancer and hormone receptor-positive, HER2-negative breast cancer.
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 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).
AstraZeneca and Daiichi Sankyo have Phase III trials evaluating datopotamab deruxtecan-based combinations as potential 1st-line treatment options for patients with advanced or metastatic NSCLC without actionable genomic alterations compared to the respective standard of care for the patient population of each study.
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AVANZAR is evaluating datopotamab deruxtecan plus Imfinzi and carboplatin in patients regardless of PD-L1 expression or tumour histology.
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TROPION-Lung01 is evaluating datopotamab deruxtecan Versus Docetaxel in Previously Treated Advanced or Metastatic Non-small Cell Lung Cancer With or Without Actionable Genomic Alterations (AGAs)
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TROPION-Lung07 is evaluating datopotamab deruxtecan plus pembrolizumab with or without chemotherapy in patients with non-squamous disease and PD-L1 expression less than 50%.
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TROPION-Lung08 is evaluating datopotamab deruxtecan plus pembrolizumab in patients with PD-L1 expression of 50% or greater.
Beyond the TROPION programme, datopotamab deruxtecan is also being evaluated in novel combinations in several ongoing trials. AstraZeneca is also researching a potential diagnostic test to help identify patients most likely to benefit from treatment with datopotamab deruxtecan.
The Company’s comprehensive portfolio includes leading lung cancer medicines and the next wave of innovations, including Tagrisso (osimertinib) and Iressa (gefitinib); Imfinzi (durvalumab) and Imjudo (tremelimumab); Enhertu (trastuzumab deruxtecan) and datopotamab deruxtecan in collaboration with Daiichi Sankyo; Orpathys (savolitinib) in collaboration with HUTCHMED; as well as a pipeline of potential new medicines and combinations across diverse mechanisms of action.
Source: Press Release