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 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 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 endeavor 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.
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 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 programs 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 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 AstraZeneca and Daiichi
Sankyo entered into a global collaboration to jointly develop and
commercialize fam-trastuzumab deruxtecan-nxki 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 fam-trastuzumab
deruxtecan-nxki 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
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.
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 catalyze 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 is a global, science-led
biopharmaceutical company that focuses on the discovery,
development, and commercialization 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 www.astrazeneca-us.com and follow
us on social media @AstraZeneca.
References
- Cancer.net. Lung Cancer - Non-Small Cell: Statistics. Available
at:
https://www.cancer.net/cancer-types/lung-cancer-non-small-cell/statistics#:~:text=NSCLC%20is%20the%20most%20common,be%20diagnosed%20with%20lung%20cancer.
Accessed February 2024.
- 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.
- 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.
- 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.
- 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
Cell Lung Cancer. Available at:
https://www.cancer.org/cancer/types/lung-cancer/treating-non-small-cell/targeted-therapies.html.
Accessed February 2024.
US-86131 Last Updated 2/24
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Brendan McEvoy +1 302 885 2677 Chelsea Tressler +1 302 885 2677
US Media Mailbox: usmediateam@astrazeneca.com
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