Datopotamab deruxtecan Biologics License Application accepted in the US for patients with previously treated advanced nonsquamous non-small cell lung cancer
Application based on results from the TROPION-Lung01 Phase III trial
If approved,
The BLA is based on results from the pivotal TROPION-Lung01 Phase III trial in which datopotamab deruxtecan demonstrated a statistically significant improvement for the dual primary endpoint of progression-free survival (PFS) compared to docetaxel, the current standard of care, in patients with locally advanced or metastatic NSCLC treated with at least one prior line of therapy. For the dual primary endpoint of overall survival (OS), interim results numerically favored datopotamab deruxtecan over docetaxel in the overall population; however, results did not reach statistical significance at the time of data cut-off. In patients with nonsquamous NSCLC, datopotamab deruxtecan showed a clinically meaningful PFS benefit and a numerically favorable OS trend. The trial is ongoing and OS will be assessed at final analysis.
Datopotamab deruxtecan is a specifically engineered TROP2-directed DXd antibody drug conjugate (ADC) being jointly developed by
Results from TROPION-Lung01 were presented during a Presidential Symposium at the 2023
The safety profile of datopotamab deruxtecan was consistent with that observed in other ongoing trials with no new safety concerns identified.
A parallel BLA for datopotamab deruxtecan based on results from the pivotal TROPION-Breast01 Phase III trial is pending acceptance in the US for the treatment of adult patients with metastatic hormone receptor (HR)-positive, HER2-negative (IHC 0, IHC 1+ or IHC 2+/ISH-) breast cancer. Additional regulatory submissions for datopotamab deruxtecan in lung and breast cancer are underway globally.
Advanced non-small cell lung cancer
Nearly 250,000 lung cancer cases were diagnosed in the US in 2023.1 NSCLC is the most common type of lung cancer accounting for about 80% of cases.1 Approximately 70% and 30% of NSCLC tumors are of nonsquamous or squamous histology, respectively.2 While immunotherapy and targeted therapies have improved outcomes in the 1st-line setting, most patients eventually experience disease progression and receive chemotherapy.3-5 For decades, chemotherapy has been the last treatment available for patients with advanced NSCLC, despite limited effectiveness and known side effects.3-5
TROP2 is a protein broadly expressed in the majority of NSCLC tumors.6 There is currently no TROP2-directed ADC approved for the treatment of lung cancer.7,8
TROPION-Lung01
TROPION-Lung01 is an ongoing global, randomized, multicenter, open-label Phase III trial evaluating the efficacy and safety of datopotamab deruxtecan versus docetaxel in patients with locally advanced or metastatic NSCLC with and without actionable genomic alterations previously treated with at least one prior line of therapy. Patients with actionable genomic alterations were previously treated with platinum-based chemotherapy and an approved targeted therapy. Patients without known actionable genomic alterations were previously treated, concurrently or sequentially, with platinum-based chemotherapy and a PD-1 or PD-L1 inhibitor.
The dual primary endpoints of TROPION-Lung01 are PFS as assessed by blinded independent central review (BICR) and overall survival. Key secondary endpoints include investigator-assessed PFS, objective response rate, duration of response, time to response, disease control rate as assessed by both BICR and investigator, and safety. TROPION-Lung01 enrolled approximately 600 patients in
Datopotamab deruxtecan (Dato-DXd)
Datopotamab deruxtecan (Dato-DXd) is an investigational TROP2-directed ADC. Designed using Daiichi Sankyo’s proprietary DXd ADC Technology, datopotamab deruxtecan is one of six ADCs in the oncology pipeline of Daiichi Sankyo, and one of the most advanced programs in AstraZeneca’s ADC scientific platform. Datopotamab deruxtecan is comprised of a humanized anti-TROP2 IgG1 monoclonal antibody, developed in collaboration with
A comprehensive development program called TROPION is underway globally with more than 14 trials evaluating the efficacy and safety of datopotamab deruxtecan across multiple cancers, including NSCLC, triple-negative breast cancer and HR-positive, HER2-negative breast cancer. Beyond the TROPION program, datopotamab deruxtecan also is being evaluated in novel combinations in several ongoing trials.
Daiichi Sankyo collaboration
The Company’s comprehensive portfolio includes leading lung cancer medicines and the next wave of innovations, including osimertinib and gefitinib; durvalumab and tremelimumab; fam-trastuzumab deruxtecan-nxki and datopotamab deruxtecan in collaboration with Daiichi Sankyo; savolitinib in collaboration with HUTCHMED; as well as a pipeline of potential new medicines and combinations across diverse mechanisms of action.
The Company’s focus is on some of the most challenging cancers. It is through persistent innovation that
References
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National Cancer Institute . SEER Cancer Statistics Factsheets: Lung and Bronchus Cancer, 2015. Available at: SEER Cancer Statistics Factsheets: Lung and Bronchus Cancer, 2015. AccessedFebruary 2024 . - Chen R, et al. Emerging therapeutic agents for advanced non-small cell lung cancer. J Hematol Oncol. 2020;13(1):58.
- Majeed U, et al. Targeted therapy in advanced non-small cell lung cancer: current advances and future trends. J Hematol Oncol. 2021;14(1):108.
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Pircher, A, et al. Docetaxel in the Treatment of Non-small Cell
Lung Cancer (NSCLC) – An Observational Study Focusing on Symptom Improvement.Anticancer Research . 2013;33(9):3831-3836. - Mito R, et al. Clinical impact of TROP2 in non‐small lung cancers and its correlation with abnormal p53 nuclear accumulation. Pathol Int. 2020;70(5):287-294.
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Rodríguez-Abreau D et al. Pemetrexed plus platinum with or without pembrolizumab in patients with previously untreated metastatic nonsquamous NSCLC: protocol-specified final analysis from KEYNOTE-189.
Ann Onc . 2021 Jul;32(7): 881-895. -
American Cancer Society . Targeted Drug Therapy for Non-Small CellLung Cancer . Available at: https://www.cancer.org/cancer/types/lung-cancer/treating-non-small-cell/targeted-therapies.html. AccessedFebruary 2024 .
US-86131 Last Updated 2/24
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