This announcement contains inside
information
27 May 2024
Datopotamab deruxtecan showed
clinically meaningful overall survival
improvement vs. chemotherapy
in patients with advanced nonsquamous
non-small cell lung cancer in
TROPION-Lung01 Phase III trial
In the overall trial
population, survival results numerically favoured AstraZeneca
and
Daiichi Sankyo's datopotamab
deruxtecan but did not reach statistical
significance
TROPION-Lung01 previously met
the dual primary endpoint
of progression-free survival
in the overall trial population
Results support applications
currently under review by
regulatory authorities
globally including in the US and EU
High-level overall survival (OS)
results from the TROPION-Lung01
Phase III trial, which previously met the dual
primary endpoint of progression-free survival (PFS), numerically
favoured datopotamab deruxtecan (Dato-DXd) compared to docetaxel in
the overall trial population of patients with locally advanced or
metastatic non-small cell lung cancer (NSCLC) treated with at least
one prior line of therapy. Survival results did not reach
statistical significance in the overall trial population. In the
prespecified subgroup of patients with nonsquamous NSCLC,
datopotamab deruxtecan showed a clinically meaningful improvement
in OS compared to docetaxel, the current standard-of-care
chemotherapy.
The final analysis of OS builds on
the positive progression-free survival (PFS) results
presented at the 2023 European Society
for Medical Oncology Congress which showed datopotamab deruxtecan
demonstrated a statistically significant improvement in PFS in the
overall trial population and a clinically meaningful PFS benefit in
patients with nonsquamous NSCLC. In TROPION-Lung01, patient
enrolment by tumour histology was balanced across treatment arms
and consistent with real-world incidence with approximately 75% of
patients having nonsquamous NSCLC.1,2
The safety profile of datopotamab
deruxtecan in TROPION-Lung01 was consistent with the previous
analysis including fewer dose reductions or discontinuations due to
adverse events compared to docetaxel, and no new safety concerns
identified. No new interstitial lung disease events of any grade
were adjudicated as drug-related.
Susan Galbraith, Executive Vice
President, Oncology R&D, AstraZeneca, said: "Datopotamab deruxtecan is the only investigational therapy to
show a clinically meaningful survival improvement in patients with
previously treated nonsquamous non-small cell lung cancer versus
docetaxel, which has long been unsurpassed in this post-targeted
treatment and post-immunotherapy setting. These results reinforce
the potential for datopotamab deruxtecan to replace conventional
chemotherapy in this late-line setting and underscore our
confidence in ongoing trials evaluating this therapy in first-line
lung cancer."
Ken Takeshita, MD, Global Head,
R&D, Daiichi Sankyo, said: "The
improvement in overall survival seen with datopotamab deruxtecan
coupled with the previously reported clinically meaningful
progression-free survival, more than doubling of overall response
and prolonged duration of response compared to docetaxel suggest
that this TROP2-directed antibody drug conjugate could potentially
become an important new treatment for patients with nonsquamous
non-small cell lung cancer in this advanced setting. These data
will support our ongoing discussions with regulatory authorities
globally to potentially bring datopotamab deruxtecan to patients as
quickly as possible and mark another step forward in creating new
standards of care for patients with cancer."
Datopotamab deruxtecan is a
specifically engineered TROP2-directed DXd antibody drug conjugate
discovered by Daiichi Sankyo and being jointly developed by
AstraZeneca and Daiichi Sankyo.
The data will be presented at a
forthcoming medical meeting and will support regulatory
applications currently under review globally, including in the US
and EU for the treatment of adult patients with locally advanced or
metastatic nonsquamous NSCLC who have received prior systemic
therapy.
Notes
Advanced non-small cell lung cancer
Nearly 2.5 million lung cancer cases
were diagnosed globally in 2022.3 NSCLC is the most
common type of lung cancer, accounting for about 80% of
cases.4 Approximately 75% and 25% of NSCLC tumours are
of nonsquamous or squamous histology,
respectively.1 While
immunotherapy and targeted therapies have improved outcomes in the
1st-line setting, most patients eventually experience disease
progression and receive chemotherapy.5-7 For decades,
chemotherapy has been the last treatment available for patients
with advanced NSCLC, despite limited effectiveness and known side
effects.5-7
TROP2 is a protein broadly expressed
in the majority of NSCLC tumours.8 There is currently no
TROP2-directed ADC approved for the treatment of lung
cancer.9,10
TROPION-Lung01
TROPION-Lung01 is a global,
randomised, multicentre, open-label Phase III trial evaluating the
efficacy and safety of datopotamab deruxtecan (6.0mg/kg) versus
docetaxel (75mg/m2) 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 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 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.
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
and HR-positive, HER2-negative breast cancer.
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. National Cancer
Institute. SEER Cancer Statistics Factsheets:
Lung and Bronchus Cancer, 1975-2017. Accessed May 2024.
2. Ahn M-J, et al. Datopotamab deruxtecan
(Dato-DXd) vs doxetaxel in previously treated advanced/metastatic
(adv/met) non-small cell lung cancer (NSCLC): results of the
randomized phase 3 study TROPION-Lung01. Presented at: ESMO
Congress 2023, 20-24 October 2023; Madrid, Spain. LBA12.
3. 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 May 2024.
4. 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 May 2024.
5. Chen
R, et al. Emerging
therapeutic agents for advanced non-small cell lung cancer.
J Hematol Oncol.
2020;13(1):58.
6. 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.
7. 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.
8. 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.
9. 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.
10. 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 May 2024.
Adrian Kemp
Company
Secretary
AstraZeneca
PLC