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 October 2020
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.
Enhertu granted Priority
Review in the US for the treatment of HER2-positive
metastatic gastric cancer
28 October 2020 07:00 GMT
Enhertu granted Priority Review in the US for
the
treatment of HER2-positive metastatic gastric cancer
Only HER2-directed medicine to demonstrate significant improvement
in overall survival compared to chemotherapy for
previously treated patients in this setting
AstraZeneca and Daiichi Sankyo Company, Limited (Daiichi
Sankyo)'s Enhertu (trastuzumab deruxtecan) has received
acceptance for its supplemental Biologics License Application
(sBLA) and has also been granted Priority Review in the US for the
treatment of patients with HER2-positive metastatic gastric or
gastroesophageal junction (GEJ) adenocarcinoma.
The Food and Drug Administration (FDA) grants Priority Review to
applications for medicines that offer significant advances over
available options by demonstrating safety or efficacy improvements,
preventing serious conditions, or enhancing patient compliance. The
Prescription Drug User Fee Act date, the FDA action date for their
regulatory decision, will be during the first quarter of
2021.
There are more than 27,000 new cases of gastric cancer in the US
each year, of which approximately one in five are HER2
positive.1,2 For
patients with metastatic gastric cancer who progress on initial
treatment with an anti-HER2 medicine, there are no other approved
HER2-directed medicines.
José Baselga, Executive Vice President, Oncology R&D,
said: "Once patients with HER2-positive metastatic gastric cancer
progress following initial treatment with an anti-HER2 regimen,
there are no approved HER2-directed medicines. The prognosis for
these patients is poor, as available treatment options offer only
limited clinical benefit. This milestone brings us one step closer
to delivering a potentially practice-changing medicine to patients
with gastric cancer in the US."
Antoine Yver, Executive Vice President and Global Head, Oncology
Research and Development, Daiichi Sankyo, said: "The results of the
DESTINY-Gastric01 trial are unprecedented as they represent the
first time a HER2-directed medicine has demonstrated an improvement
in survival following chemotherapy and HER2 treatment in the
metastatic setting. Building on the recent Breakthrough Therapy
Designation, the filing of the application and Priority Review by
the FDA for this potential new indication
for Enhertu reflects the importance of the data and the
significant unmet need for patients with previously treated
HER2-positive metastatic gastric cancer."
The sBLA was based on results from the DESTINY-Gastric01 randomised
Phase II trial, which demonstrated a statistically significant and
clinically meaningful improvement in objective response rate (ORR),
the primary endpoint, and overall survival (OS), a key secondary
endpoint, for patients treated with Enhertu versus chemotherapy (paclitaxel or
irinotecan monotherapy).
The safety and tolerability profiles of Enhertu in DESTINY-Gastric01 were consistent with
that observed in the gastric cancer cohort of the Phase I trial and
previously reported Enhertu trials in other tumours.3 The
most common Grade 3 or higher treatment-emergent adverse events
were decreased neutrophil count, anaemia, decreased white blood
cell count and decreased appetite. There were 12 (9.6%) cases of
confirmed treatment-related interstitial lung disease (ILD) or
pneumonitis in 125 patients treated with Enhertu as determined by an independent review
committee. The majority of cases were Grade 1 or 2 with two Grade
3, one Grade 4 and no Grade 5 (ILD-related
deaths).
The results from the trial were presented during the American
Society of Clinical Oncology ASCO20 Virtual Scientific Program and
simultaneously published online in The
New England Journal of Medicine in May 2020.4
Enhertu received Breakthrough Therapy
Designation from the FDA
in May 2020 for patients with unresectable or metastatic
HER2-positive gastric or GEJ adenocarcinoma who have received two
or more prior regimens including trastuzumab
and Orphan Drug
Designation for patients
with gastric cancer, including GEJ
adenocarcinoma. Enhertu has not been approved in the US for gastric
or GEJ adenocarcinoma.
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.5,6 In
the US, it is estimated that 27,600 new cases of gastric cancer
will be diagnosed in 2020 and more than 11,000 people will die from
the disease.1
Approximately one in five gastric cancers are HER2
positive.2 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 metastatic gastric cancer that
progresses on 1st-line treatment, there are no other approved
HER2-targeted medicines.8
DESTINY-Gastric01
DESTINY-Gastric01 is a 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-positive (defined as IHC3+ or IHC2+/ISH+), advanced gastric or
GEJ adenocarcinoma 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. OS, a key secondary endpoint, was to be
evaluated hierarchically at a prespecified interim analysis if the
primary endpoint was statistically significant. Additional efficacy
endpoints include progression-free survival, duration of response,
disease control rate 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 is comprised of a HER2 monoclonal antibody
attached to a topoisomerase I inhibitor payload by a
tetrapeptide-based linker.
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 in the
metastatic setting based on the DESTINY-Breast01 trial, and is
under accelerated assessment in the EU for HER2-positive metastatic
breast cancer. In September 2020, Enhertu (6.4mg/kg) was approved in Japan for
patients with HER2-positive unresectable advanced or recurrent
gastric cancer that progressed after
chemotherapy.
Enhertu clinical
development
|
Clinical development programme for Enhertu
|
|
Name
|
Phase
|
Population
|
Design
|
|
Breast cancer
|
|
DESTINY-Breast01
|
II
|
HER2-positive
unresectable and/or metastatic breast cancer previously treated
withtrastuzumab emtansine
|
Enhertu
|
|
DESTINY-Breast02
|
III
|
HER2-positive
unresectable and/or metastatic breast cancer previously treated
withtrastuzumab emtansine
|
Enhertu vs.
investigator's
choice chemotherapy
|
|
DESTINY-Breast03
|
III
|
HER2-positive
unresectable and/or metastatic breast cancer previously treated
with trastuzumab and taxane
|
Enhertu vs. trastuzumab emtansine
|
|
DESTINY-Breast04
|
III
|
HER2-low
unresectable and/or metastatic breast cancer previously treated
with one or two therapies
|
Enhertu vs.
investigator's
choice chemotherapy
|
|
DESTINY-Breast06a,b
|
III
|
HER2-low
unresectable and/or metastatic breast cancer previously treated
with endocrine therapy
|
Enhertu vs.
investigator's
choice chemotherapy
|
|
DESTINY-Breast07a,b
|
I/II
|
HER2-positive
metastatic breast cancer
|
Enhertu in combination with Imfinzi (durvalumab), paclitaxel
or pertuzumab
|
|
DESTINY-Breast08a,b
|
I
|
HER2-low
metastatic breast cancer
|
Enhertu in combination with capecitabine, capivasertib,
anastrozole, Faslodex (fulvestrant) or Imfinzi
and paclitaxel
|
|
BEGONIAb,c
|
I/II
|
Metastatic
triple negative breast cancer
|
Imfinzi in combination with paclitaxel
and Imfinzi in
combination with either Enhertu, capivasertib, or
oleclumab with or without paclitaxel
|
|
Gastric cancer
|
|
DESTINY-Gastric01
|
II
|
HER2-positive
locally advanced or metastatic gastric cancer and/or
gastroesophageal junction (GEJ) adenocarcinoma previously treated
with two or more lines of therapy
|
Enhertu vs. investigator's choice
chemotherapy
|
|
DESTINY-Gastric02
|
II
|
HER2-positive
unresectable and/or metastatic gastric cancer or GEJ adenocarcinoma
previously treated with a trastuzumab-containing
regime
|
Enhertu
|
|
DESTINY-Gastric03a,b
|
II
|
HER2-positive
advanced or metastatic gastric cancer or GEJ
adenocarcinoma
|
Enhertu monotherapy
or in
combination with chemotherapy
and/or Imfinzi
|
|
Lung cancer
|
|
DESTINY-Lung01
|
II
|
HER2
mutant or overexpressing unresectable and/or
metastatic
non-squamous
non-small cell lung cancer (NSCLC) previously treated with one or
more systemic therapies
|
Enhertu
|
|
HUDSONb,c
|
II
|
Metastatic
NSCLC previously treated with anti-PD-1/PD-L1 therapy
|
Umbrella
trial of Imfinzi in combination with
either Enhertu, Lynparza, AZD9150,
AZD6738,
vistusertib,
oleclumab or cediranib
|
|
Other or non-tumour specific
|
|
DESTINY-CRC01
|
II
|
HER2-expressing
RAS/BRAF-wild type unresectable and/or metastatic
colorectal
cancer previously treated with two or more lines of
therapy
|
Enhertu
|
|
DESTINY-PanTumor02a,b
|
II
|
HER2-expressing
solid tumours (bladder, biliary tract, cervical, endometrial,
ovarian cancer, pancreatic and rare tumours)
|
Enhertu
|
|
NCT04042701
(U106)
|
Ib
|
Locally-advanced/metastatic
breast or NSCLC
|
Enhertu in combination with pembrolizumab
|
|
NCT03523572
(U105)
|
Ib
|
HER2-expressing
breast and urothelial cancer who had disease progression during or
after prior therapies, did not respond to standard therapies, or
for whom no standard therapy is available
|
Enhertu in combination with nivolumab
|
|
NCT03523572 (J101)
|
I
|
Advanced
solid malignant tumours
|
Enhertu
|
aTrials led by
AstraZeneca bNew
trials that have been added to the clinical development programme
and have achieved FPCD cEnhertu arm
added to ongoing AstraZeneca trial.
Collaboration between AstraZeneca and Daiichi Sankyo
AstraZeneca and Daiichi Sankyo entered into a global collaboration
to jointly develop and commercialise Enhertu (a HER2-directed ADC) in March 2019, and
DS-1062 (a TROP2-directed ADC) in July 2020, except in Japan where
Daiichi Sankyo maintains exclusive rights. Daiichi Sankyo is
responsible for manufacturing and supply
of Enhertu and
DS-1062.
AstraZeneca in gastrointestinal cancers
AstraZeneca has a broad development programme for the treatment of
gastrointestinal (GI) cancers across several medicines spanning a
variety of tumour types and stages of disease. In 2018, GI cancers
collectively represented nearly five million new cancer cases
leading to more than 3.5 million deaths.5 Within
this programme, the Company is committed to improving outcomes in
gastric, liver, oesophageal, pancreatic, and colorectal
cancers.
The Company aims to understand the potential
of Enhertu in the two most common GI cancers,
colorectal and gastric cancers.5 Lynparza (olaparib)
is a first-in-class PARP inhibitor with a broad and advanced
clinical trial programme across multiple GI tumour types including
pancreatic and colorectal cancers. Lynparza is developed and commercialised in
collaboration with MSD (Merck & Co., Inc. inside the US and
Canada). Imfinzi (durvalumab) is being assessed both as
monotherapy and in combinations including with tremelimumab across
the two main types of liver cancer, hepatocellular carcinoma and
biliary tract cancer, and in oesophageal and gastric
cancers.10
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 seven 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.
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.
AstraZeneca
AstraZeneca (LSE/STO/Nasdaq: 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. American
Cancer Society. Stomach Cancer: About Stomach Cancer. Available
at: https://www.cancer.org/cancer/stomach-cancer/about/key-statistics.html.
2. American
Cancer Society. Stomach Cancer: Treating Stomach Cancer. Available
at: https://www.cancer.org/cancer/stomach-cancer/treating/targeted-therapies.html.
3. 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.
4. Shitara, K et al. Trastuzumab
Deruxtecan in Previously Treated HER2-Positive Gastric
Cancer. N Engl J
Med. 2020;382(25):2419-2430. DOI:
10.1056/NEJMoa2004413.
5. 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.
6. 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.
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
10. Hilmi, M et al. Immune Therapy for
Liver Cancers. Cancers (Basel) 2020 Jan; 12(1):
77.
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:
28 October
2020
|
|
By: /s/
Adrian Kemp
|
|
|
Name:
Adrian Kemp
|
|
|
Title:
Company Secretary
|