REG - AstraZeneca PLC - Dato-DXd significantly improved PFS in lung cancer

AstraZenecaAnnouncement

03/07/2023 07:00

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RNS Number : 7141E  AstraZeneca PLC  03 July 2023

This announcement contains inside information

 

3 July 2023

 

Datopotamab deruxtecan met dual primary endpoint of

progression-free survival in patients with advanced

non-small cell lung cancer in TROPION-Lung01 Phase III trial

 

First Phase III results for AstraZeneca and Daiichi Sankyo's TROP2-directed
antibody drug conjugate demonstrated statistically significant

improvement in progression-free survival vs. standard chemotherapy

in previously treated locally advanced or metastatic disease

 

Trial will continue to assess the dual primary endpoint of overall survival

 

Positive high-level results from the TROPION-Lung01 Phase III trial showed
datopotamab deruxtecan (Dato-DXd) demonstrated a statistically significant
improvement for the dual primary endpoint of progression-free survival (PFS)
compared to docetaxel, the current standard of care chemotherapy, in patients
with locally advanced or metastatic non-small cell lung cancer (NSCLC) treated
with at least one prior therapy.

 

For the dual primary endpoint of overall survival (OS), the data were not
mature and an early trend was observed in favour of datopotamab deruxtecan
versus docetaxel that did not meet the prespecified threshold for statistical
significance at this interim analysis. The trial will continue as planned to
assess OS with greater maturity. The investigators and participants will
remain blinded to the results.

 

The safety profile of datopotamab deruxtecan was consistent with previous
clinical trials with no new safety signals identified. All grade interstitial
lung disease was generally consistent with prior clinical trials, with the
majority being low grade. Some Grade 5 events were observed.

 

Datopotamab deruxtecan is a specifically engineered TROP2-directed DXd
antibody drug conjugate (ADC) being jointly developed by AstraZeneca and
Daiichi Sankyo.

 

Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca,
said: "With TROPION-Lung01, we met the dual primary endpoint of
progression-free survival, challenging the entrenched standard of care in a
previously treated and unselected patient population that has long deserved an
alternative to chemotherapy. These first Phase III trial results from the
datopotamab deruxtecan clinical programme provide compelling evidence for the
potential role this TROP2-directed antibody drug conjugate can play in
treating patients with lung cancer."

 

Ken Takeshita, MD, Global Head, Oncology R&D, Daiichi Sankyo, said: "We
are encouraged by the statistically significant results of the dual primary
endpoint of progression-free survival seen with datopotamab deruxtecan and
look forward to the final overall survival analysis. We plan to share these
data with regulatory authorities to discuss next steps."

 

More than one million people worldwide are diagnosed with advanced NSCLC each
year.(1,2) While immunotherapy and targeted therapies have improved outcomes
in the 1st-line metastatic 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 in the
absence of other treatment options and despite limited effectiveness and known
side effects.(3-5) TROP2 is a protein highly expressed in a large majority of
lung cancers. There are currently no TROP2-directed ADCs approved for the
treatment of patients with lung cancer.(6-8)

( )

TROPION-Lung01 enrolled patients with and without actionable genomic
alterations, such as EGFR and ALK. Patients with actionable genomic
alterations were previously treated with platinum-based chemotherapy and an
approved targeted therapy. Patients without actionable genomic alterations
were previously treated, concurrently or sequentially, with platinum-based
chemotherapy and a PD-1 or PD-L1 inhibitor.

 

The data will be presented at a forthcoming medical meeting and shared with
health authorities.

Notes

 

Non-small cell lung cancer

More than one million people worldwide are diagnosed with advanced NSCLC each
year.(1,2) While immunotherapy and targeted therapies have improved outcomes
in the 1st-line metastatic 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 in the
absence of other treatment options and despite limited effectiveness and known
side effects.(3-5)

( )

TROP2 is a protein highly expressed in a large majority of lung cancers.(6)
There are currently no TROP2-directed ADCs approved for the treatment of
patients with lung cancer.(7,8)

 
TROPION-Lung01

TROPION-Lung01 is a global, randomised, multicentre, open-label Phase III
trial evaluating the efficacy and safety of datopotamab deruxtecan (6.0 mg/kg)
versus docetaxel (75 mg/m(2)) in patients with locally advanced or metastatic
NSCLC, with or without actionable genomic alterations, treated with at least
one prior therapy. Patients without actionable genomic alterations were
previously treated, concurrently or sequentially, with platinum-based
chemotherapy and a prior PD-1 or PD-L1 inhibitor. Patients with actionable
genomic alterations were previously treated with platinum-based chemotherapy
and targeted therapy as approved for their detected genomic alteration.

 

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 and disease control rate as assessed by both BICR and an
investigator, and safety.

 

TROPION-Lung01 enrolled approximately 600 patients at sites 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 five lead 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, via tetrapeptide-based cleavable linkers.

 

A comprehensive development programme is underway globally with more than 12
trials evaluating the efficacy and safety of datopotamab deruxtecan across
multiple TROP2-targetable tumours, including NSCLC, triple-negative breast
cancer and hormone receptor-positive, HER2-low or negative breast cancer.
Beyond the TROPION programme, datopotamab deruxtecan is also being evaluated
in novel combinations in several ongoing trials.

 

In NSCLC, the TROPION-Lung07, TROPION-Lung08 and AVANZAR Phase III trials are
evaluating datopotamab deruxtecan and immune checkpoint inhibitor combinations
as potential 1st-line treatment options for patients with advanced or
metastatic disease, a strategy informed by the results of two early trials.
AstraZeneca is also researching a potential diagnostic test to help identify
patients most likely to benefit from treatment with datopotamab deruxtecan.

 

AstraZeneca and 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)
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#!)
, 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 Twitter @AstraZeneca (https://twitter.com/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
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.

 

References

1.   Siegel R, et al. Cancer Statistics, 2021. CA Cancer J Clin.
2021;71:7-33.

2.   World Health Organization. International Agency for Research on Cancer.
Lung Fact Sheet. Available at:
https://gco.iarc.fr/today/data/factsheets/cancers/15-Lung-fact-sheet.pdf
(https://gco.iarc.fr/today/data/factsheets/cancers/15-Lung-fact-sheet.pdf) .
Accessed July 2023.

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. 2013;33(9):3831-3836.

6.   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.

7.   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.

8.   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 July 2023.

 

Adrian Kemp
Company Secretary
AstraZeneca PLC

 

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