24 December 2024
Datopotamab deruxtecan
application in the EU for patients with advanced
nonsquamous
non-small cell
lung cancer voluntarily withdrawn
AstraZeneca and Daiichi Sankyo have voluntarily
withdrawn the marketing authorisation application (MAA) in the EU
for datopotamab deruxtecan (Dato-DXd) for the treatment of adult
patients with locally advanced or metastatic nonsquamous non-small
cell lung cancer (NSCLC) based on the TROPION-Lung01
Phase III trial.
The decision to withdraw the MAA was informed by
feedback from the Committee for Medicinal Products for Human Use of
the European Medicines Agency (EMA). AstraZeneca and Daiichi
Sankyo will continue to work to bring datopotamab deruxtecan
to patients with lung cancer in the EU who can benefit and are
committed to unlocking the potential of this medicine in lung
cancer through our robust clinical development programme which
includes seven pivotal trials in various lung cancer settings.
AstraZeneca and Daiichi Sankyo's application in the
EU for datopotamab deruxtecan for the treatment of hormone receptor
(HR)-positive, HER2-negative metastatic breast cancer based on the
TROPION-Breast01
Phase III trial remains under review.
Datopotamab deruxtecan is a specifically engineered
TROP2-directed DXd antibody drug conjugate (ADC) discovered by
Daiichi Sankyo and being jointly developed by AstraZeneca and
Daiichi Sankyo.
Notes
Advanced
non-small cell lung cancer
Nearly 2.5 million lung cancer cases were
diagnosed globally in 2022.1 In Europe, nearly half a
million lung cancer cases were diagnosed in 2022.1 Lung
cancer is broadly split into small or non-small cell lung cancer,
the latter accounting for about 80% of cases.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 tumours.6 There is currently no
TROP2-directed ADC approved for the treatment of lung
cancer.7,8
TROPION-Lung01
TROPION-Lung01
is a global, randomised, multicentre, open-label Phase III
trial evaluating the efficacy and safety of datopotamab deruxtecan
versus docetaxel in adult patients with locally advanced or
metastatic NSCLC with and without actionable genomic alterations
who require systemic therapy following prior treatment. Patients
with actionable genomic alterations were previously treated with an
approved targeted therapy and platinum-based chemotherapy. 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 progression-free survival (PFS) as assessed by blinded
independent central review (BICR) and overall survival (OS). Key
secondary endpoints include investigator-assessed PFS, objective
response rate, duration of response, time to response, and disease
control rate as assessed by both BICR and investigator, and
safety.
TROPION-Lung01 enrolled approximately 600
patients in Asia, Europe, North America, Oceania and South America.
For more information visit ClinicalTrials.gov.
Primary results from TROPION-Lung01, as
presented at the European Society for Medical
Oncology 2023 Congress, showed datopotamab deruxtecan demonstrated
a statistically significant improvement in PFS over docetaxel. OS
results were
presented at the IASLC 2024 World
Conference on Lung Cancer hosted by the International Association
for the Study of Lung Cancer and simultaneously
published
in the Journal of Clinical
Oncology in September 2024.
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 DXd ADCs in the oncology pipeline of Daiichi Sankyo, and one of
the most advanced programmes in AstraZeneca's ADC scientific
platform. Datopotamab deruxtecan is comprised of a humanised
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.
Datopotamab deruxtecan has been
granted Breakthrough Therapy Designation by the US
Food and Drug Administration for the treatment of adult patients
with locally advanced or metastatic epidermal growth factor
receptor-mutated (EGFRm)
NSCLC with disease progression on or after treatment with an
EGFR-tyrosine kinase
inhibitor and platinum-based chemotherapy. AstraZeneca and Daiichi
Sankyo have submitted a Biologics License Application for
datopotamab deruxtecan for this potential indication.
Datopotamab
deruxtecan clinical development programme
A comprehensive global clinical development programme
is underway with more than 20 trials evaluating the efficacy and
safety of datopotamab deruxtecan across multiple cancers, including
NSCLC, triple-negative breast cancer (TNBC) and HR-positive,
HER2-negative breast cancer. The programme includes seven Phase III
trials in lung cancer and five Phase III trials in breast cancer
evaluating datopotamab deruxtecan as a monotherapy and in
combination with other anticancer treatments in various
settings.
Daiichi Sankyo
collaboration
AstraZeneca and Daiichi
Sankyo entered into a global collaboration to jointly develop and
commercialise Enhertu (trastuzumab deruxtecan)
in March
2019 and datopotamab deruxtecan
in July
2020, except in Japan where Daiichi Sankyo
maintains exclusive rights for each ADC. Daiichi Sankyo is
responsible for the manufacturing and supply of Enhertu and datopotamab
deruxtecan.
AstraZeneca in lung
cancer
AstraZeneca is working to bring patients with
lung cancer closer to cure through the detection and treatment of
early-stage disease, while also pushing the boundaries of science
to improve outcomes in the resistant and advanced settings. By
defining new therapeutic targets and investigating innovative
approaches, the Company aims to match medicines to the patients who
can benefit most.
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 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.
AstraZeneca is a founding member of the Lung Ambition
Alliance, a global coalition working to accelerate innovation and
deliver meaningful improvements for people with lung cancer,
including and beyond treatment.
AstraZeneca in
oncology
AstraZeneca is leading a revolution in oncology
with the ambition to provide cures for cancer in every form,
following the science to understand cancer and all its complexities
to discover, develop and deliver life-changing medicines to
patients.
The Company's focus is on some of the most
challenging cancers. It is through persistent innovation that
AstraZeneca has built one of the most diverse portfolios and
pipelines in the industry, with the potential to catalyse changes
in the practice of medicine and transform the patient
experience.
AstraZeneca has the vision to redefine cancer care
and, one day, eliminate cancer as a cause of death.
AstraZeneca
AstraZeneca
(LSE/STO/Nasdaq: AZN) is a global, science-led biopharmaceutical
company that focuses on the discovery, development, and
commercialisation of prescription medicines in Oncology, Rare
Diseases, and BioPharmaceuticals, including Cardiovascular, Renal
& Metabolism, and Respiratory & Immunology. Based in
Cambridge, UK, AstraZeneca's innovative medicines are sold in more
than 125 countries and used by millions of patients worldwide.
Please visit astrazeneca.com and
follow the Company on social media @AstraZeneca.
Contacts
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References
1.
World Health Organization. Global Cancer
Observatory: Lung. Available at:
https://gco.iarc.who.int/media/globocan/factsheets/cancers/15-trachea-bronchus-and-lung-fact-sheet.pdf.
Accessed December 2024.
2.
American Cancer Society. Key Statistics for Lung
Cancer. Available at:
https://www.cancer.org/cancer/types/lung-cancer/about/key-statistics.html#:~:text=NSCLC%20is%20the%20most%20common,be%20diagnosed%20with%20lung%20cancer.
Accessed December 2024.
3.
Chen R, et al. Emerging therapeutic agents for
advanced non-small cell lung cancer. J Hematol Oncol.
2020:13(1):58.
4.
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.
5.
Pircher A, et al. Docetaxel in the treatment of
non-small cell lung cancer (NSCLC) - an observational study
focusing on symptom improvement. Anticancer Research.
2020;70(5):287-294.
6.
Mito R, et al. Clinical impact of TROP2 in
non-small cell lung cancers and its correlationn with abnormal p53
nuclear accumulation. Pathol Int.
2020;70(5):287-294.
7.
American Cancer Society. Targeted Drug Therapy for
Non-Small Cell Lung Cancer. Available at:
https://www.cancer.org/cancer/types/lung-cancer/treating-non-small-cell/targeted-therapies.html.
Accessed December 2024.
8.
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.
Adrian
Kemp
Company Secretary
AstraZeneca
PLC
