REG - AstraZeneca PLC - Dato-DXd improved OS in nonsquamous lung cancer

AstraZenecaAnnouncement

28/05/2024 07:00

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RNS Number : 9394P  AstraZeneca PLC  28 May 2024

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
(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)
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/m(2)) 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
(https://clinicaltrials.gov/ct2/show/NCT04656652) .

 

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
(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
(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 (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.   National Cancer Institute. SEER Cancer Statistics Factsheets: Lung and
Bronchus Cancer, 1975-2017.
(https://url.de.m.mimecastprotect.com/s/PhyOCvQnzwu4X2RYJhQuaao?domain=seer.cancer.gov)
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
(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
(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.
(https://www.cancer.org/cancer/types/lung-cancer/treating-non-small-cell/targeted-therapies.html.%20Accessed%20May%202023)
Accessed May 2024.

 

Adrian Kemp
Company Secretary
AstraZeneca PLC

 

 

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