AstraZeneca and Daiichi Sankyo’s
[fam]-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 [fam]-trastuzumab
deruxtecan (DS-8201), an investigational 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 [fam]-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 (range: 13.8 -
16.9) and median progression-free survival of 16.4 months (range:
12.7 - not reached). The median overall survival (OS) has not yet
been reached with an estimated survival rate for patients receiving
[fam]-trastuzumab deruxtecan 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 [fam]-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
[fam]-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 [fam]-trastuzumab
deruxtecan prompted a high level of durable tumor 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 (%)iii
6.0
PR (%)iii
54.9
SD (%)iii
36.4
PD (%)
1.6
DCR (%)iii
97.3 (93.8-99.1)
CBR (%)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 program at the 2019
San Antonio Breast Cancer Symposium (SABCS) and simultaneously
published in The New England Journal of Medicine.
Prior therapies included ado-trastuzumab emtansine (T-DM1)
(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 was 10 months
(range: 0.7 - 20.5 months) with a median duration of follow-up of
11.1 months (range: 0.7 - 19.9). As of data cut-off on August 1,
2019, 42.9% of patients remained on-treatment.
The safety and tolerability profile of [fam]-trastuzumab
deruxtecan in DESTINY-Breast01 was consistent with that observed in
the Phase I trial. The most common treatment- emergent adverse
events (TEAEs), Grade 3 or higher, were decreased neutrophil count
(20.7%), anemia (8.7%), nausea (7.6%), decreased white blood 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%), no Grade 4 events. Four deaths (2.2%) were
determined to be due to ILD.
Regulatory submission of [fam]-trastuzumab deruxtecan for the
treatment of patients with HER2-positive metastatic breast cancer
was recently accepted by the US Food and Drug Administration.
– ENDS –
NOTES TO EDITORS
About HER2-Positive Breast Cancer
Approximately one in five breast cancers are HER2 positive.
Despite recent improvements and approvals of new medicines, there
remain significant clinical needs for patients with HER2-positive
metastatic breast cancer. This disease remains incurable with
patients eventually progressing after available treatment.
Additionally, there are currently no approved HER2-targeted
medicines for HER2 FISH negative, IHC 2+ or IHC 1+ tumors.
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 poorer prognosis in patients with breast
cancer. To be considered HER2 positive, tumor cancer cells are
usually tested by one of two methods: immunohistochemistry (IHC) or
fluorescent in situ hybridization (FISH). IHC test results are
reported as: 0, IHC 1+, IHC 2+, or IHC 3+. A finding of IHC 3+
and/or FISH amplification is considered positive.
About DESTINY-Breast01
DESTINY-Breast01 is a pivotal phase II, single-arm, open-label,
global, multicenter, two-part trial evaluating the safety and
efficacy of DS-8201 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. Enrollment into DESTINY-Breast01 was completed in
September 2018 with 184 patients at more than 100 sites across
North America, Europe, Japan and other countries in Asia.
About [Fam]-trastuzumab deruxtecan
[Fam]-trastuzumab deruxtecan, (DS-8201), is the lead product in
the investigational ADC Franchise of the Daiichi Sankyo Cancer
Enterprise and the most advanced program 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 program 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 commercialize [fam-]
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, we
are committed to advance New Oncology as one of AstraZeneca’s five
Growth Platforms focused on lung, ovarian, breast and blood
cancers. In addition to our core capabilities, we actively pursue
innovative partnerships and investments that accelerate the
delivery of our strategy, as illustrated by our investment in
Acerta Pharma in hematology.
By harnessing the power of four scientific platforms –
Immuno-Oncology, Tumor Drivers and Resistance, DNA Damage Response
and Antibody Drug Conjugates – and by championing the development
of personalized combinations, AstraZeneca has the vision to
redefine cancer treatment and one day eliminate cancer as a cause
of death.
About AstraZeneca
AstraZeneca is a global, science-led biopharmaceutical company
that focuses on the discovery, development and commercialization of
prescription medicines, primarily for the treatment of diseases in
three therapy areas - Oncology, Cardiovascular, Renal &
Metabolism and Respiratory. AstraZeneca operates in over 100
countries and its innovative medicines are used by millions of
patients worldwide. For more information, please visit
www.astrazeneca-us.com and follow us on Twitter @AstraZenecaUS.
PP-US-8201a-XXXX
12/19
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