REG - AstraZeneca PLC - Dato-DXd NSQ NSCLC application withdrawn in EU

AstraZenecaAnnouncement

24/12/2024 07:00

For best results when printing this announcement, please click on link below:
https://newsfile.refinitiv.com/getnewsfile/v1/story?guid=urn:newsml:reuters.com:20241224:nRSX1961Ra&default-theme=true

RNS Number : 1961R  AstraZeneca PLC  24 December 2024

 

 

24 December 2024

 

Datopotamab deruxtecan application in the EU for patients with advanced

nonsquamous non-small cell lung cancer voluntarily withdrawn

 

AstraZeneca and Daiichi Sankyo have voluntarily withdrawn the marketing
authorisation application (MAA) in the EU for datopotamab deruxtecan
(Dato-DXd) for the treatment of adult patients with locally advanced or
metastatic nonsquamous non-small cell lung cancer (NSCLC) based on the
TROPION-Lung01 (https://clinicaltrials.gov/study/NCT04656652) Phase III trial.

 

The decision to withdraw the MAA was informed by feedback from the Committee
for Medicinal Products for Human Use of the European Medicines Agency (EMA).
AstraZeneca and Daiichi Sankyo will continue to work to bring datopotamab
deruxtecan to patients with lung cancer in the EU who can benefit and are
committed to unlocking the potential of this medicine in lung cancer through
our robust clinical development programme which includes seven pivotal trials
in various lung cancer settings.

 

AstraZeneca and Daiichi Sankyo's application in the EU for datopotamab
deruxtecan for the treatment of hormone receptor (HR)-positive, HER2-negative
metastatic breast cancer based on the TROPION-Breast01
(https://clinicaltrials.gov/study/NCT05104866) Phase III trial remains under
review.

 

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.

 

Notes

 

Advanced non-small cell lung cancer

Nearly 2.5 million lung cancer cases were diagnosed globally in 2022.(1) In
Europe, nearly half a million lung cancer cases were diagnosed in 2022.(1)
Lung cancer is broadly split into small or non-small cell lung cancer, the
latter accounting for about 80% of cases.(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 (https://clinicaltrials.gov/study/NCT04656652) is a global,
randomised, multicentre, open-label Phase III trial evaluating the efficacy
and safety of datopotamab deruxtecan versus docetaxel 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 an approved
targeted therapy and platinum-based chemotherapy. 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 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, duration of response, time to response, and 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 (https://clinicaltrials.gov/study/NCT04656652) .

 

Primary results from TROPION-Lung01, as presented
(https://www.astrazeneca.com/media-centre/press-releases/2023/datopotamab-deruxtecan-improved-progression-free-survival-vs-chemotherapy-in-tropion-lung01-phase-iii-trial.html)
at the European Society for Medical Oncology 2023 Congress, showed datopotamab
deruxtecan demonstrated a statistically significant improvement in PFS over
docetaxel. OS results were presented
(https://www.astrazeneca.com/media-centre/press-releases/2024/dato-dxd-showed-median-overall-survival-of-146-months-in-patients-with-advanced-nsclc-in-tropion-lung01-phase-iii-trial.html)
at the IASLC 2024 World Conference on Lung Cancer hosted by the International
Association for the Study of Lung Cancer and simultaneously published
(https://ascopubs.org/doi/10.1200/JCO-24-01544) in the Journal of Clinical
Oncology in September 2024.

 

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.

 

Datopotamab deruxtecan has been granted
(https://www.astrazeneca.com/media-centre/press-releases/2024/datopotamab-deruxtecan-granted-breakthrough-therapy-designation-us-patients-previously-treated-advanced-egfr-mutated-non-small-cell-lung-cancer.html)
Breakthrough Therapy Designation by the US Food and Drug Administration for
the treatment of adult patients with locally advanced or metastatic epidermal
growth factor receptor-mutated (EGFRm) NSCLC with disease progression on or
after treatment with an EGFR-tyrosine kinase inhibitor and platinum-based
chemotherapy. AstraZeneca and Daiichi Sankyo have submitted a Biologics
License Application for datopotamab deruxtecan for this potential indication.

 

Datopotamab deruxtecan clinical development programme

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 (TNBC)
and HR-positive, HER2-negative breast cancer. The programme includes seven
Phase III trials in lung cancer and five Phase III trials in breast cancer
evaluating datopotamab deruxtecan as a monotherapy and in combination with
other anticancer treatments in various settings.

 

Daiichi Sankyo collaboration
AstraZeneca and Daiichi Sankyo entered into a global collaboration to jointly
develop and commercialise Enhertu (trastuzumab deruxtecan) 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 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 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's innovative medicines are
sold in more than 125 countries and 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
For details on how to contact the Investor Relations Team, please click here
(https://www.astrazeneca.com/investor-relations.html#Contacts) . For Media
contacts, click here (https://www.astrazeneca.com/media-centre/contacts.html)
.

 

References

1.     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
(https://gco.iarc.who.int/media/globocan/factsheets/cancers/15-trachea-bronchus-and-lung-fact-sheet.pdf)
. Accessed December 2024.

2.     American Cancer Society. Key Statistics for Lung Cancer. Available
at:
https://www.cancer.org/cancer/types/lung-cancer/about/key-statistics.html#:~:text=NSCLC%20is%20the%20most%20common,be%20diagnosed%20with%20lung%20cancer
(https://www.cancer.org/cancer/types/lung-cancer/about/key-statistics.html#:~:text=NSCLC%20is%20the%20most%20common,be%20diagnosed%20with%20lung%20cancer)
.  Accessed December 2024.

3.     Chen R, et al. Emerging therapeutic agents for advanced non-small
cell lung cancer. J Hematol 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.     Mito R, et al. Clinical impact of TROP2 in non-small cell lung
cancers and its correlationn with abnormal p53 nuclear accumulation. Pathol
Int. 2020;70(5):287-294.

7.     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 December 2024.

8.     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.

 

Adrian Kemp

Company Secretary

AstraZeneca PLC

 

This information is provided by RNS, the news service of the London Stock Exchange. RNS is approved by the Financial Conduct Authority to act as a Primary Information Provider in the United Kingdom. Terms and conditions relating to the use and distribution of this information may apply. For further information, please contact
rns@lseg.com (mailto:rns@lseg.com)
 or visit
www.rns.com (http://www.rns.com/)
.

RNS may use your IP address to confirm compliance with the terms and conditions, to analyse how you engage with the information contained in this communication, and to share such analysis on an anonymised basis with others as part of our commercial services. For further information about how RNS and the London Stock Exchange use the personal data you provide us, please see our
Privacy Policy (https://www.lseg.com/privacy-and-cookie-policy)
.   END  MSCUOARRSOUUUUA