TIDMAZN
RNS Number : 5491W
AstraZeneca PLC
11 December 2019
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 results(i)
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.
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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
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END
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