REG - AstraZeneca PLC - Dato-DXd improved PFS in breast cancer

AstraZenecaAnnouncement

22/09/2023 07:00

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RNS Number : 3493N  AstraZeneca PLC  22 September 2023

This announcement contains inside information

 

22 September 2023

 

Datopotamab deruxtecan demonstrated statistically significant and clinically
meaningful progression-free survival benefit in patients with HR-positive,

HER2-low or negative breast cancer in TROPION-Breast01 Phase III trial

 

First Phase III results in breast cancer for AstraZeneca

and Daiichi Sankyo's datopotamab deruxtecan

 

Plans for global regulatory submissions underway

 

Positive high-level results from the TROPION-Breast01 Phase III trial showed
datopotamab deruxtecan (Dato-DXd) demonstrated a statistically significant and
clinically meaningful improvement for the primary endpoint of progression-free
survival (PFS) compared to investigator's choice of chemotherapy in patients
with inoperable or metastatic hormone receptor (HR)-positive, HER2-low or
negative (IHC 0, IHC 1+ or IHC 2+/ISH-) breast cancer previously treated with
endocrine-based therapy and at least one systemic therapy.

 

A trend in improvement for the dual primary endpoint of overall survival (OS)
was observed for datopotamab deruxtecan versus chemotherapy. Data for OS were
not mature at this interim analysis and the trial will continue as planned to
assess OS.

 

The safety profile of datopotamab deruxtecan was consistent with previous
clinical trials in breast cancer with no new safety signals identified. All
grade interstitial lung disease rates were low.

 

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: "Today's TROPION-Breast01 news is a significant development for patients
with HR-positive, HER2-low or negative metastatic breast cancer whose tumours
have become insensitive to endocrine therapy and who currently face poor
outcomes. We are encouraged by these positive results."

 

Ken Takeshita, MD, Global Head, Oncology R&D, Daiichi Sankyo, said: "The
positive topline results from TROPION-Breast01 demonstrate the potential for
datopotamab deruxtecan to become an important treatment option for patients
with HR-positive, HER2-low or HER2-negative breast cancer in the second-line
metastatic setting. We look forward to realising the full potential of this
TROP2-directed antibody drug conjugate across breast cancer subtypes through
our ongoing Phase III programme, including two trials in patients with
triple-negative breast cancer."

 

More than two million people worldwide are diagnosed with breast cancer each
year.(1) HR-positive, HER2-low or negative breast cancer is the most common
subtype, accounting for more than 65% of diagnosed cases.(1,2) Standard
initial treatment for these patients is endocrine therapy but most patients
with advanced disease will develop resistance, underscoring the need for
additional options.(3,4) TROP2 is a protein broadly expressed in HR-positive,
HER2-low or negative breast cancer.(5,6)

 

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

 

AstraZeneca and Daiichi Sankyo have two additional Phase III trials evaluating
datopotamab deruxtecan in breast cancer. TROPION-Breast02 is comparing
datopotamab deruxtecan to chemotherapy in patients with previously untreated
locally recurrent inoperable or metastatic triple negative breast cancer
(TNBC) who are not candidates for anti-PDL1 therapy. TROPION-Breast03 is
evaluating datopotamab deruxtecan with and without Imfinzi (durvalumab) versus
investigator's choice of therapy in patients with Stage I-III TNBC with
residual disease after neoadjuvant therapy.

 

Notes

 

HR-positive breast cancer

Breast cancer is the most common cancer in the world and a leading cause of
cancer-related death.(1) More than two million breast cancer cases were
diagnosed in 2020 with nearly 685,000 deaths globally.(1)

 

Breast cancer is considered HR-positive, HER2-low or negative when tumours
test positive for oestrogen and/or progesterone hormone receptors and negative
or low for HER2 (measured as HER2 score of IHC 0, IHC 1+ or IHC 2+/ISH-).(2,7)
HR-positive, HER2-low or negative breast cancer is the most common subtype,
accounting for more than 65% of diagnosed cases.(2) Approximately 30% of
patients diagnosed with HR-positive, HER2-low or negative metastatic breast
cancer are expected to live five years after their diagnosis.(2)

 

TROP2 is a protein broadly expressed in several solid tumours, including HR
positive, HER2-low or negative breast cancer.(5) TROP2 expression is
associated with increased tumour progression and poor survival in patients
with breast cancer.(5,6)

 

TROPION-Breast01

TROPION-Breast01 is global, randomised, multicentre, open-label Phase III
trial evaluating the safety and efficacy of datopotamab deruxtecan versus
investigator's choice of single-agent chemotherapy (eribulin, capecitabine,
vinorelbine or gemcitabine) in patients with inoperable or metastatic HR-
positive, HER2-low or negative (IHC 0, IHC 1+ or IHC 2+/ISH-) breast cancer
who have previously progressed on or are not suitable for endocrine therapy
per investigator assessment.

 

The dual primary endpoints of TROPION-Breast01 are PFS as assessed by blinded
independent central review (BICR) and OS. Key secondary endpoints include
objective response rate, duration of response, investigator-assessed PFS,
disease control rate and time to first subsequent therapy.

 

TROPION-Breast01 enrolled more than 700 patients at sites in Asia, Europe,
North America, South America and Africa. For more information visit
ClinicalTrials.gov
(https://clinicaltrials.gov/study/NCT05104866?term=tropiion-breast01&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 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, DXd) 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 tumours, including non-small cell lung cancer, 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. AstraZeneca is also
researching a potential diagnostic test to help identify patients most likely
to benefit from treatment with datopotamab deruxtecan.

 

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 breast cancer

Driven by a growing understanding of breast cancer biology, AstraZeneca is
starting to challenge, and redefine, the current clinical paradigm for how
breast cancer is classified and treated to deliver even more effective
treatments to patients in need - with the bold ambition to one day eliminate
breast cancer as a cause of death.

 

AstraZeneca has a comprehensive portfolio of approved and promising compounds
in development that leverage different mechanisms of action to address the
biologically diverse breast cancer tumour environment.

 

With Enhertu (trastuzumab deruxtecan), a HER2-directed ADC, AstraZeneca and
Daiichi Sankyo are aiming to improve outcomes in previously treated
HER2-positive and HER2-low metastatic breast cancer and are exploring its
potential in earlier lines of treatment and in new breast cancer settings.

 

In HR-positive breast cancer, AstraZeneca continues to improve outcomes with
foundational medicines Faslodex (fulvestrant) and Zoladex (goserelin) and aims
to reshape the HR-positive space with next-generation SERD and potential new
medicine camizestrant as well as a potential first-in-class AKT kinase
inhibitor, capivasertib. AstraZeneca is also collaborating with Daiichi Sankyo
to explore the potential of TROP2-directed ADC, datopotamab deruxtecan, in
this setting.

 

PARP inhibitor Lynparza (olaparib) is a targeted treatment option that has
been studied in early and metastatic breast cancer patients with an inherited
BRCA mutation. AstraZeneca with MSD (Merck & Co., Inc. in the US and
Canada) continues to research Lynparza in these settings and to explore its
potential in earlier disease.

 

To bring much-needed treatment options to patients with triple-negative breast
cancer, an aggressive form of breast cancer, AstraZeneca is evaluating the
potential of datopotamab deruxtecan alone and in combination with
immunotherapy Imfinzi, capivasertib in combination with chemotherapy, and
Imfinzi in combination with other oncology medicines, including Lynparza and
Enhertu.

 

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.   Sung H, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of
Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer
J Clin. 2021; 10.3322/caac.21660.

2.   National Cancer Institute. Surveillance, Epidemiology and End Results
Program. Available at:
https://seer.cancer.gov/statfacts/html/breast-subtypes.html
(https://seer.cancer.gov/statfacts/html/breast-subtypes.html) . Accessed
September 2023.

3.   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.

4.   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.

5.   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.

6.   Vidula N, et al. Trophoblast Cell Surface Antigen 2 gene (TACSTD2)
expression in primary breast cancer. Breast Cancer Res Treat. 2022
Aug;194(3):569-575.

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

 

Adrian Kemp
Company Secretary
AstraZeneca PLC

 

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