- In the overall trial population, survival results numerically
favored Daiichi Sankyo and AstraZeneca’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 the U.S. and EU
Topline overall survival (OS) results from the TROPION-Lung01
phase 3 trial, which previously met the dual primary endpoint of
progression-free survival (PFS), numerically favored datopotamab
deruxtecan (Dato-DXd) compared to docetaxel in the overall trial
population of adult 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 pre-specified
subgroup of patients with nonsquamous NSCLC, datopotamab deruxtecan
showed a clinically meaningful improvement in OS compared to
docetaxel, the current standard of care chemotherapy.
Datopotamab deruxtecan is a specifically engineered TROP2
directed DXd antibody drug conjugate discovered by Daiichi Sankyo
(TSE: 4568) and being jointly developed by Daiichi Sankyo and
AstraZeneca (LSE/STO/Nasdaq: AZN).
The final analysis of OS builds on the positive PFS results
presented at the European Society for Medical Oncology (#ESMO23)
2023 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 enrollment by tumor
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 with no new safety concerns identified. No new
interstitial lung disease events of any grade were adjudicated as
drug-related.
"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 metastatic
setting,” said Ken Takeshita, MD, Global Head, R&D, Daiichi
Sankyo. “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 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,” said Susan Galbraith,
MBBChir, PhD, Executive Vice President, Oncology R&D,
AstraZeneca. “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.”
The data will be presented at an upcoming medical meeting and
will support regulatory applications currently under review
globally, including the U.S. and EU for the treatment of adult
patients with locally advanced or metastatic nonsquamous NSCLC who
have received prior systemic therapy.
About TROPION-Lung01 TROPION-Lung01 is a global,
randomized, multicenter, open-label phase 3 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, 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 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, Oceania and South America. For more
information visit ClinicalTrials.gov.
About 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 tumors are of
nonsquamous or squamous histology, respectively.1 While
immunotherapy and targeted therapies have improved outcomes in the
first-line setting, most patients eventually experience disease
progression and receive chemotherapy.5,6,7 For decades,
chemotherapy has been the last treatment available for patients
with advanced NSCLC, despite limited effectiveness and known side
effects.5,6,7
TROP2 is a protein broadly expressed in the majority of NSCLC
tumors.8 There is currently no TROP2 directed ADC approved for the
treatment of lung cancer.9,10
About 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 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 global clinical development program 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.
About the Daiichi Sankyo and AstraZeneca Collaboration
Daiichi Sankyo and AstraZeneca entered into a global collaboration
to jointly develop and commercialize ENHERTU in March 2019 and
datopotamab deruxtecan (Dato-DXd) 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.
About the DXd ADC Portfolio of Daiichi Sankyo The DXd ADC
portfolio of Daiichi Sankyo currently consists of six ADCs in
clinical development across multiple types of cancer. ENHERTU, a
HER2 directed ADC, and datopotamab deruxtecan, a TROP2 directed
ADC, are being jointly developed and commercialized globally with
AstraZeneca. Patritumab deruxtecan (HER3-DXd), a HER3 directed ADC,
ifinatamab deruxtecan (I-DXd), a B7-H3 directed ADC, and
raludotatug deruxtecan (R-DXd), a CDH6 directed ADC, are being
jointly developed and commercialized globally with Merck & Co.,
Inc., Rahway, N.J. USA. DS-3939, a TA-MUC1 directed ADC, is being
developed by Daiichi Sankyo.
Designed using Daiichi Sankyo’s proprietary DXd ADC Technology
to target and deliver a cytotoxic payload inside cancer cells that
express a specific cell surface antigen, each ADC consists of a
monoclonal antibody attached to a number of topoisomerase I
inhibitor payloads (an exatecan derivative, DXd) via
tetrapeptide-based cleavable linkers.
Datopotamab deruxtecan, ifinatamab deruxtecan, patritumab
deruxtecan, raludotatug deruxtecan and DS-3939 are investigational
medicines that have not been approved for any indication in any
country. Safety and efficacy have not been established.
About Daiichi Sankyo Daiichi Sankyo is an innovative
global healthcare company contributing to the sustainable
development of society that discovers, develops and delivers new
standards of care to enrich the quality of life around the world.
With more than 120 years of experience, Daiichi Sankyo leverages
its world-class science and technology to create new modalities and
innovative medicines for people with cancer, cardiovascular and
other diseases with high unmet medical need. For more information,
please visit www.daiichisankyo.com.
_________________________________
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 docetaxel 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. Accessed May 2024. 4 Cancer.net. Lung Cancer –
Non-Small Cell: Statistics. Accessed May 2024. 5 Chen R, et al. J
Hematol Oncol. 2020:13(1):58. 6 Majeed U, et al. J Hematol Oncol.
2021;14(1):108. 7 Pircher A, et al. Anticancer Research.
2020;70(5):287-294. 8 Mito R, et al. Pathol Int.
2020;70(5):287-294. 9 Rodríguez-Abreau D, et al. Ann Onc. 2021
Jul;32(7):881-895. 10 American Cancer Society. Targeted Drug
Therapy for Non-Small Cell Lung Cancer. Accessed May 2024.
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Media Contacts: Global/US: Jennifer Brennan
Daiichi Sankyo, Inc. jbrennan2@dsi.com +1 908 900 3183 (mobile)
Japan: Daiichi Sankyo Co., Ltd. DS-PR@daiichisankyo.co.jp
Investor Relations Contact:
DaiichiSankyoIR@daiichisankyo.co.jp