a2284g
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 November 2022
Commission
File Number: 001-11960
AstraZeneca PLC
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AstraZeneca PLC
INDEX
TO EXHIBITS
1.
Enhertu recommended for EU approval in gastric
14
November 2022 07:10 GMT
Enhertu recommended for approval in
the EU by CHMP for patients with previously treated HER2-positive
advanced gastric cancer
Based on DESTINY-Gastric02 which showed AstraZeneca and Daiichi
Sankyo's Enhertu demonstrated clinically meaningful efficacy and
DESTINY-Gastric01 which showed improved overall survival compared
to chemotherapy
AstraZeneca
and Daiichi Sankyo's Enhertu (trastuzumab deruxtecan)
has been recommended for approval in the European Union (EU) as
monotherapy for the treatment of adult patients with advanced
HER2-positive gastric or gastroesophageal junction (GEJ)
adenocarcinoma who have received a prior trastuzumab-based
regimen.
Enhertu is a specifically engineered HER2-directed
antibody drug conjugate (ADC) being jointly developed and
commercialised by AstraZeneca and Daiichi Sankyo.
The Committee for Medicinal Products for Human Use (CHMP) of the
European Medicines Agency based its positive opinion on results
from the DESTINY-Gastric02 and the DESTINY-Gastric01 Phase II
trials.
In DESTINY-Gastric02, conducted in patients from North America and
Europe, updated results showed treatment
with Enhertu resulted in a confirmed objective response
rate (ORR) of 41.8% as assessed by independent central review
(ICR). Median duration of response (DoR) was 8.1 months and median
overall survival (OS) was 12.1 months. Primary results from
the DESTINY-Gastric02 Phase II trial were presented at the 2021
European Society for Medical
Oncology (ESMO) Congress, with the updated data presented at ESMO
2022.1
In DESTINY-Gastric01, conducted in patients from Japan and South
Korea, updated results showed treatment
with Enhertu resulted in an ORR of 51.3% versus 14.3%
with chemotherapy (irinotecan or paclitaxel). Patients treated
with Enhertu had a 40% reduction in the risk of death
versus patients treated with chemotherapy (based on a hazard ratio
of 0.60; 95% confidence interval: 0.42-0.86, p=0.01) with a median
OS of 12.5 months versus 8.9 months. Additionally, confirmed ORR, a
major efficacy outcome, was 42.0% with Enhertu versus 12.5% with chemotherapy as assessed
by ICR. The primary analysis was published
in The
New England Journal of Medicine,2 with
the updated data presented at the 2021 American Society of Clinical
Oncology Annual Meeting.
Susan Galbraith, Executive Vice President, Oncology R&D,
AstraZeneca, said: "Gastric cancer is usually diagnosed in the advanced
stage in many European countries and patients face high mortality
rates. If approved, Enhertu would
be the first HER2-directed medicine for patients with advanced
gastric cancer in the European Union in more than a
decade."
Ken Takeshita, Global Head, Oncology R&D, Daiichi
Sankyo, Inc, said: "Enhertu is
the first HER2-directed medicine to demonstrate a significant
improvement in overall survival compared to chemotherapy in
patients with gastric cancer following initial treatment with a
HER2-directed medicine in the advanced or metastatic setting. The
CHMP opinion recognises the high unmet need in this patient
population and brings us one step closer to bringing this medicine
to patients with gastric cancer in Europe."
In both trials, the safety profiles observed in patients treated
with Enhertu were consistent with those seen in other
trials of Enhertu with no new safety signals
identified.
Enhertu is approved in the
US and several other countries for locally advanced or metastatic
HER2-positive gastric cancer.
Notes
HER2-positive gastric cancer
Gastric (stomach) cancer is the fifth most common cancer worldwide
and the fourth highest leading cause of cancer mortality, with a
five-year global survival rate of 5% to 10% for advanced or
metastatic disease.3-5 Approximately
one million new patients were diagnosed with gastric cancer in
2020, with 768,000 deaths reported globally.6 In
Europe, approximately 136,000 cases of gastric cancer are diagnosed
annually, and Eastern Europe has the second highest incidence of
gastric cancer worldwide after Eastern Asia.5-6 Gastric
cancer is the sixth leading cause of cancer death in Europe and is
typically diagnosed in the advanced stage. Even when diagnosed in
earlier stages of the disease, the survival rate remains
modest.5-7
Approximately one in five gastric cancers are
HER2-positive.8,9 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.8 HER2
overexpression may be associated with a specific HER2 gene
alteration known as HER2 amplification.9
Recommended first-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.10 For
patients with metastatic gastric cancer that progresses following
initial treatment with a trastuzumab-based regimen, treatment
options are limited, and in many regions in the world there are no
additional HER2 directed medicines available.2,11,12
DESTINY-Gastric02
DESTINY-Gastric02
is an open-label, single-arm Phase II trial in Western patients
evaluating the efficacy and safety of Enhertu (6.4mg/kg) in patients
with HER2-positive metastatic and/or unresectable gastric or GEJ
adenocarcinoma with disease progression on or after a
trastuzumab-containing regimen.
The
primary endpoint of DESTINY-Gastric02 is confirmed ORR based on
ICR. Secondary endpoints include progression-free survival (PFS),
OS, DoR and safety.
DESTINY-Gastric02
enrolled 79 patients at multiple sites in North America and
Europe. For more information about the trial,
visit ClinicalTrials.gov.
DESTINY-Gastric01
DESTINY-Gastric01
is a randomised, open-label Phase II trial evaluating the efficacy
and safety of Enhertu (6.4mg/kg) in patients
from Japan and South Korea with primarily HER2-positive (defined as
immunohistochemistry [IHC] 3+ or IHC 2+/in-situ hybridisation
[ISH]+) advanced gastric cancer or GEJ adenocarcinoma whose tumours
have progressed on two or more prior treatment regimens including
fluoropyrimidine (5-FU), platinum chemotherapy and trastuzumab.
Patients were randomised 2:1 to receive Enhertu or physician's choice of
chemotherapy (paclitaxel or irinotecan monotherapy).
The
primary endpoint of DESTINY-Gastric01 is ORR. Secondary endpoints
include OS, PFS, DoR, disease control rate and time to treatment
failure, as well as pharmacokinetic and safety
endpoints.
DESTINY-Gastric01
enrolled 187 patients at multiple sites in Japan and South Korea.
For more information about the trial, visit ClinicalTrials.gov.
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 35
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 Brazil and 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 under accelerated approval
in the US for the treatment of adult patients with unresectable or
metastatic non-small cell lung cancer whose tumours have activating
HER2 (ERBB2) mutations, as detected by an FDA-approved test, and
who have received a prior systemic therapy, based on the results of
the DESTINY-Lung02 trial. Continued approval for this indication
may be contingent upon verification and description of clinical
benefit in a confirmatory 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 GEJ 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 other 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, and
datopotamab deruxtecan (DS-1062; a TROP2-directed ADC)
in July 2020,
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 gastrointestinal cancers
AstraZeneca
has a broad development programme for the treatment of
gastrointestinal (GI) cancers across several medicines and a
variety of tumour types and stages of disease. In 2020, GI cancers
collectively represented approximately 5.1 million new cancer cases
leading to approximately 3.6 million deaths.13
Within
this programme, the Company is committed to improving outcomes in
gastric, liver, biliary tract, oesophageal, pancreatic and
colorectal cancers.
Enhertu, a HER2-directed antibody drug conjugate, is
approved in the US and several other countries for HER2-positive
advanced gastric cancer and is being assessed in colorectal
cancer. Enhertu is jointly developed and
commercialised by AstraZeneca and Daiichi Sankyo.
Imfinzi (durvalumab) is approved in the US and several
other countries in combination with chemotherapy (gemcitabine plus
cisplatin) for advanced biliary tract cancer and in the US in
combination with Imjudo (tremelimumab) in
unresectable hepatocellular carcinoma. Imfinzi is being assessed in
combinations, including with Imjudo, in liver, oesophageal and
gastric cancers in an extensive development programme spanning
early to late-stage disease across settings.
Lynparza (olaparib), a first-in-class PARP inhibitor,
is approved in the US and several other countries for the
treatment of BRCA-mutated metastatic pancreatic
cancer. Lynparza is developed and
commercialised in collaboration with MSD (Merck & Co., Inc.
inside the US and Canada).
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 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. Updated analysis
of DESTINY-Gastric02. Available at: https://oncologypro.esmo.org/meeting-resources/esmo-congress/updated-analysis-of-destiny-gastric02-a-phase-ii-single-arm-trial-of-trastuzumab-deruxtecan-t-dxd-in-western-patients-pts-with-her2-positive.
Accessed November 2022.
2. Shitara K, et al. Trastuzumab Deruxtecan in
Previously Treated HER2-Positive Gastric
Cancer. N Engl J Med 2020; 382:2419-2430.
3.
Casamayor M, et al.
Targeted literature review of the global burden of gastric
cancer. Ecancermedicalscience.
2018; 12:883;12:883.
4. SEER Cancer Stat Facts: Stomach Cancer. Available
at: https://seer.cancer.gov/statfacts/html/stomach.html.
Accessed November 2022.
5. 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.
6. WHO. International Agency
of Cancer Research. Cancer Today. Stomach Incidence. 2020.
Available at: https://gco.iarc.fr/today/data/factsheets/cancers/7-Stomach-fact-sheet.pdf.
Accessed November 2022.
7. Cancer Research UK. Stomach
Cancer Survival Statistics. Available at: https://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/stomach-cancer/survival#heading-Zero.
Accessed November 2022.
8.
Iqbal N, et al. Human Epidermal Growth Factor Receptor 2
(HER2) in Cancers: Overexpression and Therapeutic
Implications. Mol Biol
Int. 2014; 2014:852748.
9. Abrahao-Machado LF, et al. HER2 testing in
gastric cancer: An update. World J
Gastroenterol. 2016;
22(19):4619-4625.
10. Orditura
M, et al. "Treatment of gastric cancer." World Journal of
Gastroenterology:
WJG 20.7 (2014): 1635.
11. Thuss-Patience PC, et al. Trastuzumab
emtansine versus taxane use for previously treated HER2-positive
locally advanced or metastatic gastric or gastro-oesophageal
junction adenocarcinoma (GATSBY): an international randomised,
open-label, adaptive, phase 2/3 study. Lancet
Oncol. 2017;
18(5):640-653.
12. Satoh T,
et al. Lapatinib Plus Paclitaxel Versus Paclitaxel Alone in the
Second-Line Treatment of HER2-Amplified Advanced Gastric Cancer in
Asian Populations: TyTAN-A Randomized, Phase III
Study. J Clin
Oncol.2014; 32(19):2039‐2049.
13. WHO.
World Cancer Fact Sheet. Available at:
https://gco.iarc.fr/today/data/factsheets/populations/900-world-fact-sheets.pdf.
Accessed November 2022.
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:
14 November 2022
|
By: /s/
Adrian Kemp
|
|
Name:
Adrian Kemp
|
|
Title:
Company Secretary
|