19 February 2024
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, AstraZeneca and Daiichi
Sankyo's datopotamab deruxtecan may be
the first TROP2-directed antibody drug
conjugate for patients with lung cancer
AstraZeneca and Daiichi Sankyo's Biologics
License Application (BLA) for datopotamab deruxtecan (Dato-DXd) has
been accepted in the US for the treatment of adult patients with
locally advanced or metastatic nonsquamous non-small cell lung
cancer (NSCLC) who have received prior systemic therapy. The
Prescription Drug User Fee Act date, the Food and Drug
Administration (FDA) action date for its regulatory decision, is
during the fourth quarter of 2024.
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 favoured 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 favourable 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 AstraZeneca and Daiichi Sankyo.
Susan Galbraith, Executive Vice President,
Oncology R&D, AstraZeneca, said: "Datopotamab deruxtecan has
the potential to offer patients with previously treated advanced
nonsquamous non-small cell lung cancer an effective and tolerable
alternative to conventional chemotherapy. With regulatory
discussions ongoing around the world and a parallel submission
underway in the US in breast cancer, this is only the beginning of
our efforts to make this novel treatment available to patients as
quickly as possible."
Ken Takeshita, MD, Global Head, R&D,
Daiichi Sankyo, said: "Today's news is an important step forward in
our goal of creating new standards of care that have the potential
to transform the treatment of patients with non-small cell lung
cancer. We are encouraged by the FDA's acceptance of the BLA as we
endeavour to make datopotamab deruxtecan the first TROP2-directed
antibody drug conjugate approved to treat patients with nonsquamous
non-small cell lung cancer after disease progression on prior
systemic therapy. We look forward to working closely with the FDA
to bring datopotamab deruxtecan to patients."
Results from
TROPION-Lung01 were presented during a Presidential Symposium
at the 2023 European Society for Medical Oncology
Congress.
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.
Notes
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 tumours 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 tumours.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,
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 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 OS. 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 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 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 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
(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.
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 operates in over 100 countries and its
innovative medicines are used by millions of patients worldwide.
Please visit astrazeneca.com and
follow the Company on social media @AstraZeneca.
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References
1.
Cancer.net, Lung Cancer - Non-Small Cell: Statistics. Available
at:
https://www.cancer.net/cancer-types/lung-cancer-non-small-cell/statistics.
Accessed February 2024.
2. National
Cancer Institute. SEER Cancer Statistics Factsheets: Lung and
Bronchus Cancer, 2015. Available at:
SEER Cancer Statistics Factsheets: Lung and Bronchus Cancer,
2015. Accessed February
2024.
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Chen R, et
al. Emerging therapeutic agents for advanced non-small cell
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Oncol. 2020;13(1):58.
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Majeed U, et
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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.
2013;33(9):3831-3836.
6. 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.
7.
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.
8. 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 February 2024.
Adrian Kemp
Company
Secretary
AstraZeneca
PLC