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 May
2020
Commission
File Number: 001-11960
AstraZeneca PLC
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AstraZeneca PLC
INDEX
TO EXHIBITS
1.
Enhertu significantly improved tumour response rate
and overall survival in HER2-positive metastatic gastric cancer in
Phase II DESTINY-Gastric01 trial
29 May 2020 13:00 BST
Enhertu significantly improved tumour response rate
and overall survival in HER2-positive metastatic gastric cancer in
Phase II DESTINY-Gastric01 trial
First HER2-directed medicine to show an improvement in overall
survival for previously treated metastatic gastric cancer with a
41% reduction in the risk of death vs. chemotherapy
Breakthrough Therapy Designation recently granted in the
US
for Enhertu in this setting
Detailed results from the positive, registrational, randomised
controlled Phase II DESTINY-Gastric01 trial showed AstraZeneca
and Daiichi Sankyo Company, Limited (Daiichi
Sankyo)'s Enhertu (trastuzumab deruxtecan) demonstrated
a statistically significant and clinically meaningful
improvement in objective response rate (ORR) and overall survival
(OS), a key secondary endpoint, versus
chemotherapy.
The trial evaluated patients with HER2-positive unresectable or
metastatic gastric or gastroesophageal junction adenocarcinoma that
had progressed following two or more treatment regimens including
trastuzumab and chemotherapy.
Gastric cancer is the third leading cause of cancer mortality with
a five-year survival rate of 5% for metastatic
disease.1,2 Approximately
one in five gastric cancers are considered HER2
positive.3,4
The confirmed ORR, assessed by independent central review, was
42.9% with Enhertu monotherapy (6.4mg/kg) compared to 12.5%
with investigator's choice of chemotherapy (paclitaxel or
irinotecan). Ten complete responses (CRs) and 41 partial
responses (PRs) were seen in patients treated
with Enhertu versus no CRs and seven PRs seen in patients
treated with chemotherapy.
Patients treated with Enhertu had a 41% reduction in the risk of death
versus patients treated with chemotherapy (based on a hazard ratio
[HR] of 0.59; 95% confidence interval [CI] 0.39-0.88; p=0.0097) at
a pre-specified interim analysis. The median OS was 12.5 months
versus 8.4 months with chemotherapy. The estimated OS rate at one
year in the Enhertu arm was 52.1% and 28.9% with the
chemotherapy arm.
Kohei Shitara, MD, Chief of Department of Gastrointestinal
Oncology, National Cancer Center Hospital East, Chiba, Japan
and principal investigator
in the Phase II DESTINY-Gastric01 trial, said: "Once patients with HER2-positive metastatic
gastric cancer progress following initial treatment with an
anti-HER2 regimen, there are limited options and no approved
HER2-targeted therapies. Based on the compelling results of the
DESTINY-Gastric01 trial, Enhertu has the potential to become a new standard
of care for these patients."
José Baselga, Executive Vice President, R&D Oncology,
said: "In DESTINY-Gastric01, the response rate was more than three
times higher with Enhertu versus chemotherapy. Additionally, more than
half of patients treated with Enhertu were alive at one year compared to less than
a third with chemotherapy. In addition to the impressive results we
saw in HER2-positive metastatic breast cancer in DESTINY-Breast01,
these results in gastric cancer may help further define the role
of Enhertu in transforming patient outcomes across
multiple HER2-targetable cancers."
Antoine Yver Executive Vice President and Global Head, Oncology
Research and Development, Daiichi Sankyo, said:
"Enhertu is
the first HER2-directed therapy to show an improvement in overall
survival for patients with previously treated HER2-positive
metastatic gastric cancer. These data are encouraging and
meaningful since patients with advanced gastric cancer have limited
therapeutic options once they progress and face markedly high
mortality rates. We are working with regulatory authorities to
bring Enhertu to patients with metastatic gastric cancer
as quickly as possible."
Enhertu showed a confirmed
disease control rate (DCR) of 85.7% versus 62.5% and a median
confirmed duration of response (DoR) of 11.3 months versus 3.9
months with chemotherapy.
Summary of results:i
|
Enhertu monotherapyii
|
Investigator's choiceof chemotherapy(paclitaxel or
irinotecan)
|
|
n=119
|
n=56
|
Confirmed ORR (%)iii,iv,v
(95%
CI)
|
42.9
(33.8-52.3; p<0.0001)
|
12.5
(5.2-24.1)
|
CR (%)
|
8.4
|
0
|
PR (%)
|
34.5
|
12.5
|
SD (%)
|
42.9
|
50.0
|
Confirmed DCR (%)vi
(95%
CI)
|
85.7
(78.1-91.5)
|
62.5(48.5-75.1)
|
Confirmed median DoR (months)
(95%
CI)
|
11.3
(5.6-NE)
|
3.9
(3.0-4.9)
|
SD, stable disease
i. Data cut-off was 8 November 2019.
ii. Enhertu 6.4mg/kg.
iii. As assessed by independent central review.
iv. ORR is (CR + PR).
v. Confirmed ORR represents responses confirmed by a follow-up scan
≥four weeks after initial CR/PR; unconfirmed ORR is the
primary endpoint of the trial (51.3% [95% CI 41.9-60.5] versus
14.3% [95% CI 6.4-26.2]; p<0.0001). Both confirmed and
unconfirmed ORR were assessed by independent central
review.
vi. DCR is (CR + PR + SD).
The safety and tolerability profile of Enhertu in DESTINY-Gastric01 was consistent with
that observed in the Phase I gastric cancer trial and previously
reported Enhertu trials.5 The
most common Grade 3 or higher treatment-emergent adverse events
were decreased neutrophil count (51.2%), anaemia (37.6%), decreased
white blood cell count (20.8%) and decreased appetite (16.8%).
There were 12 cases (9.6%) of confirmed treatment-related
interstitial lung disease (ILD) and pneumonitis as determined by an
independent review. The majority were Grade 1 or 2 with two Grade
3, one Grade 4 and no Grade 5 (ILD-related
deaths).
The results were presented during the 2020 American Society of
Clinical Oncology ASCO20 Virtual Scientific Program
and simultaneously published online
in The
New England Journal of Medicine.6
Enhertu was recently
granted Breakthrough Therapy
Designation (BTD) in the US for the treatment of patients
with HER2-positive unresectable or metastatic gastric cancer based
on data from DESTINY-Gastric01 trial and Orphan Drug
Designation (ODD) for
patients with gastric cancer, including gastroesophageal junction
cancer.
Gastric cancer
Gastric (stomach) cancer is the fifth most common cancer worldwide
and the third leading cause of cancer mortality with a five-year
survival rate of 5% for metastatic disease; there were
approximately one million new cases reported in 2018 and 783,000
deaths.1,2
Approximately one in five gastric cancers are HER2
positive.3,4 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. Gastric cancer is usually diagnosed in
the advanced stage, but even when diagnosed in earlier stages of
the disease the survival rate remains modest.7 Recommended
1st-line treatment for HER2-positive advanced or metastatic gastric
cancer is combination chemotherapy plus trastuzumab, an anti-HER2
medicine, which has been shown to improve survival outcomes when
added to chemotherapy. For gastric cancer that progresses on
1st-line treatment, there are no other approved HER2-targeted
medicines.8
DESTINY-Gastric01
DESTINY-Gastric01 is a registrational Phase II, open-label,
multi-centre, randomised controlled trial testing the safety and
efficacy of Enhertu versus investigator's choice of chemotherapy
in a primary cohort of 188 patients from Japan and South Korea with
HER2-expressing, advanced gastric cancer or gastroesophageal
junction adenocarcinoma (defined as IHC3+ or IHC2+/ISH+) who have
progressed on two or more prior treatment regimens including
fluoropyrimidine and platinum chemotherapy and trastuzumab.
Patients were randomised 2:1 to receive Enhertu or investigator's choice of chemotherapy
(paclitaxel or irinotecan monotherapy). Patients were treated
with Enhertu 6.4mg/kg once every three weeks or
chemotherapy.
The primary endpoint of the trial is ORR, as assessed by
independent central review. ORR, or tumour response rate,
represents the percentage of patients whose disease decreased
and/or disappears. OS was a key secondary endpoint to be
statistically evaluated hierarchically at a prespecified interim
analysis if the primary endpoint was statistically significant.
Other secondary endpoints include progression-free survival, DoR,
DCR and confirmed ORR assessed in those responses confirmed by a
follow-up scan of at least four weeks after initial independent
central review.9
Enhertu
Enhertu (trastuzumab
deruxtecan; fam-trastuzumab deruxtecan-nxki in the US) is a
HER2-directed antibody drug conjugate (ADC) and is the lead
ADC in the oncology portfolio of Daiichi Sankyo 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.
Enhertu (5.4mg/kg) is
approved in the US and Japan 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 DESTINY-Breast01 trial.
Enhertu clinical
development
A comprehensive development programme is underway globally with six
registrational trials evaluating the efficacy and safety
of Enhertu monotherapy across multiple HER2-targetable
cancers including breast, gastric and lung cancers. Trials in
combination with other anticancer treatments, such as
immunotherapy, are also underway.
In May 2020, Enhertu received BTD from the US FDA for the
treatment of patients with HER2-positive unresectable or metastatic
gastric or gastroesophageal junction adenocarcinoma who have
received two or more prior regimens including trastuzumab and
ODD for patients with gastric cancer, including gastroesophageal
junction cancer. In March 2018, Enhertu received a SAKIGAKE designation for
potential use in the same HER2-positive gastric cancer patient
population and a supplemental New Drug Application was recently
submitted to the Japan Ministry of Health, Labour and
Welfare.
In May 2020, Enhertu also received a BTD for the treatment of
patients with metastatic non-small cell lung cancer whose tumours
have a HER2 mutation and with disease progression on or after
platinum-based therapy.
Collaboration between AstraZeneca and Daiichi Sankyo
In March 2019, AstraZeneca and Daiichi Sankyo entered into a global
collaboration to jointly develop and
commercialise Enhertu worldwide, except in Japan where Daiichi
Sankyo maintains exclusive rights. Daiichi Sankyo is solely
responsible for manufacturing and supply.
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 six new
medicines 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 investment 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 ADCs - 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.
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 & 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 and
follow the Company on Twitter @AstraZeneca.
Contacts
For details on how to contact the Investor Relations Team, please
click here.
For Media contacts, click here.
References
1.
Bray F, et al. Global cancer statistics 2018: GLOBOCAN estimates of
incidence and mortality worldwide for 36 cancers in 185 countries.
CA Cancer J. Clin. 2018; 68:394-424.
2. American Cancer
Society. Stomach Cancer: Early Detection, Diagnosis, and Staging.
Available at: https://www.cancer.org/cancer/stomach-cancer/detection-diagnosis-staging/survival-rates.html.
3. American Cancer
Society. Stomach Cancer: Treating Stomach Cancer. Available
at: https://www.cancer.org/cancer/stomach-cancer/treating/targeted-therapies.html.
4.
Iqbal N. et al. Human Epidermal Growth Factor Receptor 2 (HER2) in
Cancers: Overexpression and Therapeutic Implications. Mol Biol Int.
2014;2014:852748. doi:10.1155/2014/852748.
5. Shitara, K, et al. Trastuzumab
deruxtecan (DS-8201a) in patients with advanced HER2-positive
gastric cancer: a dose-expansion, phase 1
study. Lancet
Oncol. 2019;
20:827-36.
6. Shitara, K et al. Trastuzumab
Deruxtecan in Previously Treated HER2-Positive Gastric
Cancer. N Engl J
Med. DOI:
10.1056/NEJMoa2004413.
7. Curea F.G, et al. Current Targeted
Therapies in HER2-Positive Gastric
Adenocarcinoma. Cancer Biotherapy &
Radiopharmaceuticals. 2017;32 (10).
8.
NCCN Guidelines® Gastric Cancer. Version 4.2019. December 20,
2019: MS-22-36.
9.
ClinicalTrials.Gov. NCT03329690. Available
at: https://www.clinicaltrials.gov/ct2/show/NCT03329690
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:
29 May
2020
|
By: /s/
Adrian Kemp
|
|
Name:
Adrian Kemp
|
|
Title:
Company Secretary
|