Blueprint
FORM 6-K
SECURITIES
AND EXCHANGE COMMISSION
Washington,
D.C. 20549
Report
of Foreign Issuer
Pursuant
to Rule 13a-16 or 15d-16 of
the
Securities Exchange Act of 1934
For the
month of December
2019
Commission
File Number: 001-11960
AstraZeneca PLC
1
Francis Crick Avenue
Cambridge
Biomedical Campus
Cambridge
CB2 0AA
United
Kingdom
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AstraZeneca PLC
INDEX
TO EXHIBITS
1.
Trastuzumab deruxtecan achieved a tumour
response rate of 60.9% in pivotal Phase II HER2-positive metastatic
breast cancer trial
11 December 2019 13:00 GMT
Trastuzumab deruxtecan achieved a tumour response rate of
60.9%
in pivotal Phase II HER2-positive metastatic breast cancer
trial
AstraZeneca and Daiichi Sankyo's trastuzumab deruxtecan
demonstrated an impressive 14.8-month
median duration of response and 16.4-month median progression-free
survival
AstraZeneca and Daiichi Sankyo Company, Limited (Daiichi
Sankyo) today presented positive detailed data from the global
pivotal Phase II single-arm DESTINY-Breast01 trial of trastuzumab
deruxtecan (DS-8201), a HER2-targeting antibody drug conjugate
(ADC) and potential new medicine, in patients with HER2-positive
metastatic breast cancer who received two or more prior
HER2-targeted regimens.
The primary endpoint of objective response rate (ORR), confirmed by
independent central review, was 60.9% with trastuzumab deruxtecan
monotherapy (5.4mg/kg). Patients had a median of six prior
therapies for metastatic disease (2-27).
Patients achieved a disease control rate (DCR) of 97.3% with a
median duration of response (DoR) of 14.8 months and median
progression-free survival (PFS) of 16.4 months. The median overall
survival (OS) has not yet been reached, with an estimated survival
rate of 86% at one year. The results were consistent across
subgroups of patients.
José Baselga, Executive Vice President, Oncology R&D,
said: "The clinically meaningful and durable responses seen among
these patients illustrate the potential of trastuzumab deruxtecan
to establish a new standard of care. These results are impressive,
as women with this advanced stage of breast cancer have already
endured multiple prior therapies for HER2-positive metastatic
breast cancer."
Antoine Yver, Executive Vice President and Global Head, Oncology
Research and Development, Daiichi Sankyo, said: "The strength of
the pivotal results and the consistency with previously reported
trastuzumab deruxtecan data further underscore that this
specifically engineered HER2-targeted antibody drug conjugate is
delivering on its intent of enhancing efficacy for patients with
HER2-positive metastatic breast cancer."
Ian E. Krop, a principal investigator of the DESTINY-Breast01 trial
and Associate Chief, Division of Breast Oncology, Susan F. Smith
Center for Women's Cancers, Dana-Farber Cancer Institute, said:
"These results are particularly striking as trastuzumab deruxtecan
prompted a high level of durable tumour reduction among patients,
the majority of whom had exhausted most if not all standard
therapies for HER2-metastatic breast cancer. We are excited by
these results and their potential to help patients with this
advanced stage of breast cancer."
Summary of resultsi
Efficacy measure
|
Total evaluable (n=184) ii
|
ORR (%)
(95% CI)
|
60.9
(53.4-68)
|
CR
(%)
|
6.0
|
PR
(%)
|
54.9
|
SD
(%)
|
36.4
|
PD
(%)
|
1.6
|
DCR (%)
(95% CI)iii
|
97.3
(93.8-99.1)
|
CBR (%)
(95% CI)iv
|
76.1
(69.3-82.1)
|
Median
DoR (95% CI)
|
14.8
months (13.8-16.9)
|
Median
PFS (95% CI)
|
16.4
months (12.7-NE)
|
Estimated
OS at 12 months (%) (95% CI)
|
86
(80-91)
|
CI, confidence interval; CR, complete response; PR, partial
response; SD, stable disease; PD, progressive disease; NE, not
estimable.
i As assessed by
independent central review.
ii 5.4mg/kg.
iii DCR is (CR + PR +
SD)
iv CBR is (CR + PR + SD
for ≥6 months)
The data were included as part of the press programme at the 2019
San Antonio Breast Cancer Symposium and simultaneously published
online in The New England Journal of
Medicine.
Prior therapies included trastuzumab emtansine (100%), trastuzumab
(100%), pertuzumab (65.8%), other anti-HER2 therapies (54.3%),
hormone therapies (48.9%) and other systemic therapies
(99.5%). Median treatment duration for trastuzumab deruxtecan
was 10 months (0.7-20.5) with a median duration of follow-up of
11.1 months (0.7-19.9). As of data cut-off on 1 August 2019, 42.9%
of patients remained on treatment.
The safety and tolerability profile of trastuzumab deruxtecan in
DESTINY-Breast01 was consistent with that observed in the Phase I
trial. The most common Grade 3 or higher treatment-emergent adverse
events were decreased neutrophil count (20.7%), anaemia (8.7%),
nausea (7.6%), decreased white cell count (6.5%), decreased
lymphocyte count (6.5%) and fatigue (6.0%). Overall, 13.6% of
patients had confirmed interstitial lung disease (ILD) related to
treatment as determined by an independent review. The events were
primarily Grade 1 or 2 (10.9%) in severity with one Grade 3 (0.5%)
and no Grade 4 events. Four deaths (2.2%) were determined to be due
to ILD.
Regulatory submission of trastuzumab deruxtecan for the treatment
of patients with HER2-positive metastatic breast cancer
was recently
accepted with Priority
Review by the US Food and Drug Administration. A regulatory
submission has also been made to Japan's Ministry of Health,
Labour and Welfare.
About HER2-positive breast cancer
Approximately one in five breast cancers are
HER2-positive.1,2 Despite
recent improvements and approvals of new medicines, there remains
significant unmet needs for patients with advanced HER2-positive
metastatic breast cancer.3,4 This
disease remains incurable with patients eventually progressing
after currently available treatments.3,4
About HER2
HER2 is a tyrosine kinase receptor growth-promoting protein found
on the surface of some cancer cells that is associated with
aggressive disease and poor prognosis in breast cancer
patients.5 To
be considered HER2-positive, tumour cancer cells are usually tested
by one of two methods: immunohistochemistry (IHC) or fluorescent in
situ hybridisation (FISH). IHC test results are reported as: 0, IHC
1+, IHC 2+, or IHC 3+.1 A
finding of IHC 3+ and/or FISH amplification is considered
positive.1
About DESTINY-Breast01
DESTINY-Breast01 is a pivotal Phase II, single-arm, open-label,
global, multicentre, two-part trial evaluating the safety and
efficacy of trastuzumab deruxtecan in patients with HER2-positive
unresectable and/or metastatic breast cancer previously treated
with trastuzumab emtansine. The primary endpoint of the trial is
objective response rate, as determined by independent central
review. Secondary objectives include duration of response, disease
control rate, clinical benefit rate, progression-free survival and
overall survival. Enrolment into DESTINY-Breast01 was completed in
September 2018 with 184 patients at more than 100 sites
globally.
About trastuzumab deruxtecan
Trastuzumab deruxtecan (DS-8201; fam-trastuzumab deruxtecan in the
US only); is the lead product in the investigational ADC Franchise
of the Daiichi Sankyo Cancer Enterprise and the most advanced
programme in AstraZeneca's ADC scientific platform. ADCs are
targeted cancer medicines that deliver cytotoxic chemotherapy
("payload") to cancer cells via a linker attached to a monoclonal
antibody that binds to a specific target expressed on cancer
cells.
A comprehensive development programme is underway in North America,
Europe and Asia, including five pivotal trials in HER2-expressing
metastatic breast and gastric cancers, including a trial in
patients with metastatic breast cancer and low levels of HER2
expression. Phase II trials are underway for HER2-expressing
advanced colorectal cancer, as well as metastatic non-squamous
HER2-overexpressing or HER2-mutated non-small cell lung cancer.
Trials in combination with other anticancer treatments, such as
immunotherapy, are also underway.
About the collaboration between AstraZeneca and Daiichi
Sankyo
In March 2019, AstraZeneca and Daiichi Sankyo entered into a global
collaboration to jointly develop and commercialise trastuzumab
deruxtecan as a potential new medicine worldwide, except in Japan
where Daiichi Sankyo maintains exclusive rights. Daiichi Sankyo is
solely responsible for manufacturing and supply.
About AstraZeneca in Oncology
AstraZeneca has a deep-rooted heritage in oncology and offers a
quickly growing portfolio of new medicines that has the potential
to transform patients' lives and the Company's future. With at
least six new medicines to be launched between 2014 and 2020, and a
broad pipeline of small molecules and biologics in development, the
Company is committed to advance oncology as a key growth driver for
AstraZeneca focused on lung, ovarian, breast and blood cancers. In
addition to AstraZeneca's main capabilities, the Company is
actively pursuing innovative partnerships and investments that
accelerate the delivery of our strategy, as illustrated by the
investment in Acerta Pharma in haematology.
By harnessing the power of four scientific platforms -
Immuno-Oncology, Tumour Drivers and Resistance, DNA Damage Response
and Antibody Drug Conjugates - and by championing the development
of personalised combinations, AstraZeneca has the vision to
redefine cancer treatment and, one day, eliminate cancer as a cause
of death.
About AstraZeneca
AstraZeneca (LSE/STO/NYSE: AZN) is a global, science-led
biopharmaceutical company that focuses on the discovery,
development and commercialisation of prescription medicines,
primarily for the treatment of diseases in three therapy areas -
Oncology, Cardiovascular, Renal and Metabolism, and Respiratory.
AstraZeneca operates in over 100 countries and its innovative
medicines are used by millions of patients worldwide. Please
visit astrazeneca.com and
follow the Company on Twitter @AstraZeneca.
Media
Relations
|
|
|
Gonzalo
Viña
|
|
+44 203
749 5916
|
Rob
Skelding
|
Oncology
|
+44 203
749 5821
|
Rebecca
Einhorn
|
Oncology
|
+1 301
518 4122
|
Matt
Kent
|
BioPharmaceuticals
|
+44 203
749 5906
|
Jennifer
Hursit
|
Other
|
+44
203 749 5762
|
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Hägerstrand
|
Sweden
|
+46 8 552 53 106
|
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Meixell
|
US
|
+1 302
885 2677
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|
Investor
Relations
|
|
|
Thomas
Kudsk Larsen
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|
+44 203
749 5712
|
Henry
Wheeler
|
Oncology
|
+44 203
749 5797
|
Christer
Gruvris
|
BioPharmaceuticals
(Cardiovascular, Metabolism)
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+44 203
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Stone
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+44 203
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References
1. Tandon A, et al. HER-2/neu Oncogene Protein and Prognosis in
Breast Cancer. J Clin
Oncol.
1989;7(8):1120-8.
2. Sledge G, et al. Past, Present, and Future Challenges in
Breast Cancer Treatment. J Clin
Oncol.
2014;32(19):1979-1986.
3. de Melo Gagliato
D, et
al. Mechanisms of Resistance
and Sensitivity to Anti-HER2 Therapies in HER2+ Breast
Cancer. Oncotarget. 2016;7(39):64431-46.
4. National
Comprehensive Cancer Network (NCCN). NCCN Guidelines. Breast
Cancer. Available at https://nccn.org.
Accessed December 2019.
5. American Cancer
Society. Breast Cancer HER2 Status. Available at https://www.cancer.org/cancer/breast-cancer/understanding-a-breast-cancer-diagnosis/breast-cancer-her2-status.html. Accessed
December 2019.
Adrian Kemp
Company Secretary
AstraZeneca PLC
SIGNATURES
Pursuant
to the requirements of the Securities Exchange Act of 1934, the
Registrant has duly caused this report to be signed on its behalf
by the undersigned, thereunto duly authorized.
Date:
11 December
2019
|
By: /s/
Adrian Kemp
|
|
Name:
Adrian Kemp
|
|
Title:
Company Secretary
|