REG - AstraZeneca PLC - EMA validates Dato-DXd MAAs for NSQ NSCLC and BC

AstraZenecaAnnouncement

04/03/2024 07:00

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RNS Number : 3665F  AstraZeneca PLC  04 March 2024

 

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
(https://www.astrazeneca.com/media-centre/press-releases/2023/datopotamab-deruxtecan-improved-progression-free-survival-vs-chemotherapy-in-tropion-lung01-phase-iii-trial.html)
and TROPION-Breast01
(https://www.astrazeneca.com/media-centre/press-releases/2023/datopotamab-deruxtecan-significantly-extended-progression-free-survival-vs-chemotherapy-in-tropion-breast01-phase-iii-trial.html)
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
(https://clinicaltrials.gov/study/NCT04656652) .

 

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
(https://clinicaltrials.gov/ct2/show/NCT05104866?term=TROPION-Breast01&draw=2&rank=1)
.

 

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
(https://www.astrazeneca.com/media-centre/press-releases/2019/astrazeneca-and-daiichi-sankyo-enter-collaboration-for-novel-her-2-targeting-antibody-drug-conjugate.html#modal-historic-confirmation)
and datopotamab deruxtecan in July 2020
(https://www.astrazeneca.com/media-centre/press-releases/2020/astrazeneca-and-daiichi-sankyo-enter-collaboration-to-develop-and-commercialise-new-antibody-drug-conjugate.html#modal-historic-confirmation)
, 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 (https://www.astrazeneca.com/) and follow the
Company on social media @AstraZeneca
(https://www.linkedin.com/company/astrazeneca/) .

 
Contacts

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(https://www.astrazeneca.com/investor-relations.html#Contacts) . For Media
contacts, click here (https://www.astrazeneca.com/media-centre/contacts.html)
.

 

References

1.   Cancer.net. Lung Cancer - Non-Small Cell: Statistics. Available at:
https://www.cancer.net/cancer-types/lung-cancer-non-small-cell/statistics
(https://www.cancer.net/cancer-types/lung-cancer-non-small-cell/statistics) .
Accessed March 2024.

2.   National Cancer Institute. SEER Cancer Statistics Factsheets: Lung and
Bronchus Cancer, 2015. Available at:
https://seer.cancer.gov/archive/csr/1975_2012/results_merged/sect_15_lung_bronchus.pdf
(https://seer.cancer.gov/archive/csr/1975_2012/results_merged/sect_15_lung_bronchus.pdf)
. Accessed March 2024.

3.   Chen R, et al. Emerging therapeutic agents for advanced non-small cell
lung cancer. J Hemal Oncol. 2020;13(1):58.

4.   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.

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. 2020;70(5): 287-294.

6.   Globocan 2022. Europe. Available at:
https://gco.iarc.who.int/media/globocan/factsheets/populations/908-europe-fact-sheet.pdf
(https://gco.iarc.who.int/media/globocan/factsheets/populations/908-europe-fact-sheet.pdf)
. Accessed March 2024.

7.   National Cancer Institute. SEER cancer stat facts: female breast cancer
subtypes. Available at:
https://seer.cancer.gov/statfacts/html/breast-subtypes.html
(https://seer.cancer.gov/statfacts/html/breast-subtypes.html) . Accessed March
2024.

8.   Iqbal N, et al. Human Epidermal Growth Factor Receptor 2 (HER2) in
Cancers: Overexpression and Therapeutic Implications. Mol Biol Int.
2014;852748.

9.   Lin M, et al. Comparative Overall Survival of CDK4/6 Inhibitors Plus
Endocrine Therapy vs. Endocrine Therapy Alone for Hormone receptor-positive,
HER2-negative metastatic breast cancer. J Cancer. 2020; 10.7150/jca.48944.

10.  Lloyd M R, et al. Mechanisms of Resistance to CDK4/6 Blockade in
Advanced Hormone Receptor-positive, HER2-negative Breast Cancer and Emerging
Therapeutic Opportunities. Clin Cancer Res. 2022; 28(5): 821-30.

11.  Goldenberg D, et al. The emergence of trophoblast cell-surface antigen 2
(TROP-2) as a novel cancer target. Oncotarget. 2018;9(48): 28989-29006.

12.  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.

13.  Vidula N, et al. Sacituzumab govitecan: Antibody-drug conjugate in
triple negative breast cancer and other solid tumours. Breast Cancer Res
Treat. 2022 Aug;194(3): 569-575.

14.  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.

15.  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
(https://www.cancer.org/cancer/types/lung-cancer/treating-non-small-cell/targeted-therapies.html)
. Accessed March 2024.

 

Adrian Kemp
Company Secretary
AstraZeneca PLC

 

 

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