4 March 2024
Two datopotamab deruxtecan
applications validated in the EU for
patients with advanced
nonsquamous non-small cell lung
cancer or HR-positive,
HER2-negative breast cancer
Parallel applications based on
TROPION-Lung01 and TROPION-Breast01 Phase III trial results
demonstrating AstraZeneca and Daiichi Sankyo's datopotamab
deruxtecan significantly improved progression-free survival vs.
chemotherapy in two types of cancer
The European Medicines Agency (EMA) has
validated two marketing authorisation applications (MAAs) for
AstraZeneca and Daiichi Sankyo's datopotamab deruxtecan (Dato-DXd)
in two types of cancer. One MAA is for the treatment of adult
patients with locally advanced or metastatic nonsquamous non-small
cell lung cancer (NSCLC) who require systemic therapy following
prior treatment. The other MAA is for the treatment of adult
patients with unresectable or metastatic hormone receptor
(HR)-positive, HER2-negative (IHC 0, IHC 1+ or IHC 2+/ISH-) breast
cancer who have progressed on and are not suitable for endocrine
therapy and received at least one additional systemic
therapy.
The validations confirm the completion of the
applications and commence the scientific review process by the
EMA's Committee for Medicinal Products for Human Use. The
applications are based on data from the pivotal
TROPION-Lung01 and
TROPION-Breast01 Phase III trials presented during two
Presidential Symposia at the 2023 European Society for Medical
Oncology Congress.
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.
Susan Galbraith, Executive Vice President,
Oncology R&D, AstraZeneca, said: "Our ambition is for
datopotamab deruxtecan to improve upon and replace conventional
chemotherapy in the treatment of multiple cancer types. Today's
dual validation of our applications in lung and breast cancers
brings this potential medicine a meaningful step closer to
redefining treatment expectations for patients with two of the most
common cancers in Europe."
Ken Takeshita, MD, Global Head, R&D,
Daiichi Sankyo, said: "The EMA validation is an important first
step toward bringing this TROP2-directed antibody drug conjugate to
eligible patients in Europe with nonsquamous lung cancer and
HR-positive, HER2-negative breast cancer. This news builds on our
recent regulatory progress in the US, where our lung cancer
application has been accepted and our breast cancer application is
underway, underscoring our commitment to changing the standard of
care by developing new medicines to help as many patients worldwide
as possible."
Additional regulatory submissions for
datopotamab deruxtecan in lung cancer and breast cancer are
underway in the US and globally.
Notes
Advanced non-small cell lung cancer
Nearly 500,000 lung cancer cases were diagnosed
in Europe in 2022.1 NSCLC is the most common type of
lung cancer, accounting for about 80% of cases.1
Approximately 70% and 30% of NSCLC tumours are of nonsquamous or
squamous histology, respectively.2 While immunotherapy
and targeted therapies have improved outcomes in the first-line
setting, most patients eventually experience disease progression
and receive chemotherapy.3,4,5 For decades, chemotherapy
has been the last treatment available for patients with advanced
NSCLC, despite limited effectiveness and known side
effects.3,4,5
HR-positive
breast cancer
More than 500,000 breast cancer cases were
diagnosed in Europe in 2022.6 HR-positive, HER2-negative
breast cancer is the most common subtype, accounting for more than
65% of diagnosed cases.7 Breast cancer is considered
HR-positive, HER2-negative when tumours test positive for oestrogen
and/or progesterone hormone receptors and negative for HER2
(measured as HER2 score of IHC 0, IHC 1+ or IHC
2+/ISH-).7,8 Standard initial treatment for this subtype
of breast cancer is endocrine therapy but most patients with
advanced disease will develop resistance, underscoring the need for
additional options.9,10
TROP2
TROP2 is a protein broadly expressed in several
solid tumours, including the majority of NSCLC and HR-positive,
HER2-negative breast cancer cases.11,12 High TROP2
expression is associated with increased tumour progression and poor
survival.12,13 There is currently no TROP2-directed ADC
approved for the treatment of lung
cancer.14,15
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 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 platinum-based chemotherapy and an approved
targeted therapy. Patients without known actionable genomic
alterations were previously treated, either in combination 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 (ORR), duration of response (DoR), time to response,
disease control rate (DCR) as assessed by both BICR and
investigator, and safety. TROPION-Lung01 enrolled approximately 600
patients in Asia, Europe, North America and South America. For more
information visit ClinicalTrials.gov.
TROPION-Breast01
TROPION-Breast01 is a global, randomised,
multicentre, open-label Phase III trial evaluating the efficacy and
safety of datopotamab deruxtecan versus investigator's choice of
single-agent chemotherapy (eribulin, capecitabine, vinorelbine or
gemcitabine) in patients with unresectable or metastatic
HR-positive, HER2-negative (IHC 0, IHC 1+ or IHC 2+/ISH-) breast
cancer who have progressed on and are not suitable for endocrine
therapy per investigator assessment and have received at least one
additional systemic therapy for unresectable or metastatic
disease.
The dual primary endpoints of TROPION-Breast01
are PFS as assessed by BICR and OS. Key secondary endpoints include
ORR, DoR, investigator-assessed PFS, DCR, time to first subsequent
therapy and safety. TROPION-Breast01 enrolled more than 700
patients in Africa, Asia, Europe, North America and South America.
For more information visit
ClinicalTrials.gov.
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 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 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
programme, datopotamab deruxtecan also is being evaluated in novel
combinations in several ongoing trials.
Daiichi Sankyo collaboration
AstraZeneca and Daiichi Sankyo entered into a
global collaboration to jointly develop and commercialise
Enhertu 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
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 operates in over 100 countries and its
innovative medicines are used by millions of patients worldwide.
Please visit astrazeneca.com and
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References
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Adrian Kemp
Company
Secretary
AstraZeneca
PLC