REG - AstraZeneca PLC - Enhertu improved PFS in mBC in DESTINY-Breast02

AstraZenecaAnnouncement

15/08/2022 07:00

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RNS Number : 9389V  AstraZeneca PLC  15 August 2022

15 August 2022 07:00 BST

 

Enhertu significantly delayed disease progression in DESTINY-Breast02

Phase III trial vs. physician's choice of treatment in patients with
HER2-positive metastatic breast cancer

 

Results consistent with previous trials, reinforcing benefit of AstraZeneca
and Daiichi Sankyo's Enhertu in previously treated patients

 

Positive high-level results from the DESTINY-Breast02 Phase III trial of
Enhertu (trastuzumab deruxtecan) versus physician's choice of treatment showed
the trial met the primary endpoint, demonstrating a statistically significant
and clinically meaningful improvement in progression-free survival (PFS) in
patients with HER2-positive unresectable and/or metastatic breast cancer
previously treated with trastuzumab emtansine (T-DM1). The trial also met the
key secondary endpoint of improved overall survival (OS).

 

Enhertu is a specifically engineered HER2-directed antibody drug conjugate
(ADC) being jointly developed and commercialised by AstraZeneca and Daiichi
Sankyo.

 

The trial evaluated a similar later-line patient population as the single-arm
DESTINY-Breast01 Phase II trial, which was the basis for initial approvals in
advanced HER2-positive metastatic breast cancer. The safety profile of Enhertu
in DESTINY-Breast02 was consistent with previous Phase III clinical trials
with no new safety concerns identified. Interstitial lung disease (ILD) rates
and severity were consistent with those observed in other metastatic breast
cancer trials of Enhertu, with a low rate of Grade 5 ILD events observed as
determined by an independent adjudication committee.

 

Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca,
said, "The DESTINY-Breast02 trial results in this patient population with
advanced disease confirm the efficacy and safety profile seen in
DESTINY-Breast01 and are consistent with the results seen across our broader
clinical programme in HER2-positive metastatic breast cancer. These data
further strengthen our confidence in Enhertu and reinforce its potential to
transform patient outcomes across multiple treatment settings."

 

Ken Takeshita, Global Head, R&D, Daiichi Sankyo, said: "The top-line
results from DESTINY-Breast02 confirm the robust progression-free survival
seen in previous trials of Enhertu and enrich our clinical understanding of
the benefit this therapy may offer patients with HER2-positive metastatic
breast cancer. As this is the confirmatory trial for our current breast cancer
indication in Europe and several other countries, we look forward to sharing
these findings with regulatory authorities to add to the body of data for
Enhertu for the treatment of HER2-positive metastatic breast cancer."

 

The data will be presented at a forthcoming medical meeting.

 

Notes

 

HER2-positive breast cancer

Breast cancer is the most common cancer and is one of the leading causes of
cancer-related deaths worldwide.(1) More than two million patients were
diagnosed with breast cancer in 2020, with nearly 685,000 deaths globally.(1)
Approximately one in five patients with breast cancer are considered
HER2-positive.(2)

 

HER2 is a tyrosine kinase receptor growth-promoting protein expressed on the
surface of many types of tumours including breast, gastric, lung and
colorectal cancers.(3) HER2 protein overexpression may occur as a result of
HER2 gene amplification and is often associated with aggressive disease and
poor prognosis in breast cancer.(4)

 

DESTINY-Breast02

DESTINY-Breast02 is a global, randomised, open-label, Phase III trial
evaluating the efficacy and safety of Enhertu (5.4mg/kg) versus physician's
choice of treatment (trastuzumab/capecitabine or lapatinib/capecitabine) in
patients with HER2-positive unresectable and/or metastatic breast cancer
previously treated with T-DM1. Patients were randomised 2:1 to receive either
Enhertu or physician's choice of treatment.

 

The primary endpoint of DESTINY-Breast02 is PFS based on blinded independent
central review (BICR). The key secondary endpoint is OS. Other secondary
endpoints include objective response rate based on BICR and investigator
assessment, duration of response based on BICR, PFS based on investigator
assessment and safety.

 

DESTINY-Breast02 enrolled approximately 600 patients at multiple sites in
Asia, Oceania, Europe, North America and South America. For more information
about the trial, visit ClinicalTrials.gov
(https://clinicaltrials.gov/ct2/show/NCT03523585?term=DESTINY-Breast02&draw=2&rank=1)
.

 

Enhertu

Enhertu is a HER2-directed ADC. Designed using Daiichi Sankyo's proprietary
DXd ADC technology, Enhertu is the lead ADC in the oncology portfolio of
Daiichi Sankyo and the most advanced programme in AstraZeneca's ADC scientific
platform. Enhertu consists of a HER2 monoclonal antibody attached to a
topoisomerase I inhibitor payload, an exatecan derivative, via a stable
tetrapeptide-based cleavable linker.

 

Enhertu (5.4mg/kg) is approved in more than 30 countries for the treatment of
adult patients with unresectable or metastatic HER2-positive breast cancer who
have received a (or one or more) prior anti-HER2-based regimen either in the
metastatic setting, or in the neoadjuvant or adjuvant setting and have
developed disease recurrence during or within six months of completing therapy
based on the results from the DESTINY-Breast03 trial.

 

Enhertu (5.4mg/kg) is approved in several countries for the treatment of adult
patients with unresectable or metastatic HER2-positive breast cancer who have
received two or more prior anti-HER2-based regimens based on the results from
the DESTINY-Breast01 trial.

 

Enhertu (5.4mg/kg) is approved in the US for the treatment of adult patients
with unresectable or metastatic HER2-low (IHC 1+ or IHC 2+/ISH-) breast cancer
who have received a prior chemotherapy in the metastatic setting or developed
disease recurrence during or within six months of completing adjuvant
chemotherapy based on the results from the DESTINY-Breast04 trial.

 

Enhertu (5.4mg/kg) is approved in the US for the treatment of adult patients
with unresectable or metastatic non-small cell lung cancer (NSCLC) whose
tumours have activating HER2 (ERBB2) mutations, as detected by a Food and Drug
Administration (FDA)-approved test, and who have received a prior systemic
therapy based on the results from the DESTINY-Lung02 trial.

 

Enhertu (6.4mg/kg) is approved in several countries for the treatment of adult
patients with locally advanced or metastatic HER2-positive gastric or
gastroesophageal junction (GEJ) adenocarcinoma who have received a prior
trastuzumab-based regimen based on the results from the DESTINY-Gastric01
trial.

 

Enhertu development programme

A comprehensive development programme is underway globally, evaluating the
efficacy and safety of Enhertu monotherapy across multiple HER2-targetable
cancers, including breast, gastric, lung and colorectal cancers. Trials in
combination with other anticancer treatments, such as immunotherapy, are also
underway.

 

Regulatory applications for Enhertu in breast and gastric cancer are currently
under review in several countries based on the DESTINY-Breast01,
DESTINY-Breast03, DESTINY-Breast04, DESTINY-Gastric01 and DESTINY-Gastric02
trials, respectively.

 

Daiichi Sankyo collaboration

Daiichi Sankyo Company, Limited (TSE: 4568) [referred to as Daiichi Sankyo]
and AstraZeneca entered into a global collaboration to jointly develop and
commercialise Enhertu (a HER2-directed ADC) 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 (DS-1062; a TROP2-directed ADC) 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. 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
challenging and redefining 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.

 

AstraZeneca aims to continue to transform outcomes for HR-positive breast
cancer with foundational medicines Faslodex (fulvestrant) and Zoladex
(goserelin) and the next-generation oral selective oestrogen receptor degrader
(SERD) and potential new medicine camizestrant.

 

PARP inhibitor Lynparza (olaparib) is a targeted treatment option that has
been studied in HER2-negative early and metastatic breast cancer patients with
an inherited BRCA mutation. AstraZeneca with MSD (Merck & Co., Inc. in the
US and Canada) continue to research Lynparza in metastatic breast cancer
patients with an inherited BRCA mutation and are exploring new opportunities
to treat these patients earlier in their disease.

 

Building on the initial approvals of Enhertu, in previously treated
HER2-positive metastatic breast cancer, AstraZeneca and Daiichi Sankyo are
exploring its potential use in earlier lines of treatment and in new breast
cancer settings.

 

To bring much needed treatment options to patients with triple-negative breast
cancer, an aggressive form of breast cancer, AstraZeneca is testing
immunotherapy Imfinzi (durvalumab) in combination with other oncology
medicines, including Lynparza and Enhertu, evaluating the potential of AKT
kinase inhibitor, capivasertib, in combination with chemotherapy, and
collaborating with Daiichi Sankyo to explore the potential of TROP2-directed
ADC, 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 (http://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
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.   Ahn S, et al. HER2 status in breast cancer: changes in guidelines and
complicating factors for interpretation. J Pathol Transl Med. 2020; 54(1):
34-44.

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

4.   Pillai R, et al. HER2 mutations in lung adenocarcinomas: A report from
the Lung Cancer Mutation Consortium. Cancer. 2017; 1; 123(21): 4099-4105.

 

Adrian Kemp

Company Secretary

AstraZeneca PLC

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