a1084q
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 2021
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.
Imfinzi improved
survival in biliary tract cancer
25 October 2021 7:00 BST
Imfinzi plus
chemotherapy significantly improved overall survival in 1st-line
advanced biliary tract cancer in TOPAZ-1 Phase III trial at interim
analysis
First immunotherapy combination to demonstrate superior clinical
outcomes
over standard of care in a global, randomised trial in this
setting
Positive high-level results from the TOPAZ-1 Phase III trial
showed Imfinzi (durvalumab), in combination with
standard-of-care chemotherapy, demonstrated a statistically
significant and clinically meaningful overall survival (OS) benefit
versus chemotherapy alone as a 1st-line treatment for patients with
advanced biliary tract cancer (BTC).
At a predefined interim analysis, the Independent Data Monitoring
Committee concluded that the trial met the primary endpoint by
demonstrating an improvement in OS in patients treated
with Imfinzi plus chemotherapy versus chemotherapy alone.
The combination also demonstrated an improvement in
progression-free survival (PFS) and overall response rate, key
secondary endpoints.
Imfinzi plus chemotherapy
was well tolerated, had a similar safety profile versus the
comparator arm and did not increase the discontinuation rate due to
adverse events compared to chemotherapy
alone.
BTC is a group of rare and aggressive cancers that occur in the
bile ducts and gallbladder.1,2 Incidence
of BTC often depends on the prevalence of common risk factors for
each type within a geographical region.
Approximately 50,000 people in the US, Europe and Japan and about
210,000 people worldwide are diagnosed with BTC each
year.3-5 These
patients have a poor prognosis, with approximately only 5% to 15%
of all patients with BTC surviving five years.4 In
December 2020, Imfinzi was granted Orphan Drug Designation in the
US for the treatment of BTC.
Do-Youn Oh, MD, PhD, Professor, Division of Medical Oncology,
Department of Internal Medicine at Seoul National University
Hospital and Seoul National University College of Medicine, and
principal investigator in the TOPAZ-1 Phase III trial, said:
"Patients with advanced biliary tract cancer are in dire need of
new treatments as progress in the 1st-line setting has remained
largely stagnant for more than 10 years. TOPAZ-1 is the first Phase
III trial to show that adding an immunotherapy to standard
chemotherapy delivers a meaningful overall survival benefit for
patients in this setting. Today's exciting results are a major step
forward in treating this disease and represent new hope for our
patients."
Susan Galbraith, Executive Vice President, Oncology R&D,
AstraZeneca, said: "We are delighted TOPAZ-1 has been unblinded
early due to clear evidence of efficacy
for Imfinzi plus
chemotherapy, which has also demonstrated a strong safety profile.
We have now delivered two positive gastrointestinal cancer trials
in a row for Imfinzi, following the HIMALAYA trial in liver cancer. We
believe the significant survival benefit demonstrated marks a new
era of immunotherapy treatment in this devastating disease, and it
advances our commitment to improving long-term survival for
patients across these cancers where treatment options are
limited."
The data will be presented at a forthcoming medical meeting and
shared with health authorities.
Notes
Biliary tract cancer
Biliary tract cancer (BTC) is a group of rare and
aggressive gastrointestinal (GI) cancers that form in the
cells of the bile ducts (cholangiocarcinoma), gallbladder or
ampulla of Vater (where the bile duct and pancreatic duct connect
to the small intestine).1,2 Cholangiocarcinoma
is more common in China and Thailand and is on the rise in Western
countries.8-10 Gallbladder
cancer is more common in certain regions of South America, India
and Japan.11,12
Apart from ampullary cancer, early-stage BTC often presents without
symptoms and most new cases of BTC are therefore diagnosed at an
advanced stage, when treatment options are limited and the
prognosis is poor.13,14
TOPAZ-1
TOPAZ-1 is a randomised, double-blind, placebo controlled,
multicentre, global Phase III trial of Imfinzi in combination with chemotherapy
(gemcitabine plus cisplatin) versus placebo in combination with
chemotherapy as a 1st-line treatment in 685 patients with
unresectable advanced or metastatic BTC including intrahepatic and
extrahepatic cholangiocarcinoma, and gallbladder cancer (ampullary
carcinoma was excluded).
The trial is being conducted in more than 145 centres across 17
countries including in the US, Europe, South America and several
countries in Asia including South Korea, Thailand, Japan, Taiwan
and China. The primary endpoint is OS and key secondary endpoints
include progression-free survival, objective response rate and
safety.
Imfinzi
Imfinzi (durvalumab) is a
human monoclonal antibody that binds to the PD-L1 protein and
blocks the interaction of PD-L1 with the PD-1 and CD80 proteins,
countering the tumour's immune-evading tactics and releasing the
inhibition of immune responses.
Imfinzi is the only
approved immunotherapy in the curative-intent setting of
unresectable, Stage III non-small cell lung cancer (NSCLC) in
patients whose disease has not progressed after chemoradiation
therapy and is the global standard of care in this setting based on
the PACIFIC Phase III trial.
Imfinzi is also approved
in the US, EU, Japan, China and many other countries around the
world for the treatment of extensive-stage small cell lung
cancer (ES-SCLC) based on the CASPIAN Phase III
trial.
Imfinzi is also approved
for previously treated patients with advanced bladder cancer in
several countries. Since the first approval in May 2017, more than
100,000 patients have been treated with Imfinzi.
As part of a broad development programme, Imfinzi is being tested as a single treatment and in
combinations with other anti-cancer treatments for patients with
SCLC, NSCLC, bladder cancer, liver cancer, BTC, oesophageal cancer,
gastric and gastroesophageal cancer, cervical cancer, ovarian
cancer, endometrial cancer, and other solid
tumours.
AstraZeneca in GI cancers
AstraZeneca has a broad development programme for the treatment of
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.15
Within this programme, the Company is committed to improving
outcomes in gastric, liver, BTC, oesophageal, pancreatic, and
colorectal cancers.
Imfinzi is being assessed
in combinations in liver, BTC, oesophageal and gastric
cancers in
an extensive development programme spanning early to late-stage
disease. In October 2021, the HIMALAYA Phase
III trial in 1st-line unresectable liver cancer met its primary
endpoint of overall survival with the STRIDE regimen, a single,
high priming dose of tremelimumab plus Imfinzi every four weeks versus
sorafenib.
The Company aims to understand the potential
of Enhertu (trastuzumab deruxtecan), a HER2-directed
antibody drug conjugate, in the two most common GI cancers,
colorectal and gastric cancers. Enhertu is jointly developed and commercialised by
AstraZeneca and Daiichi Sankyo.
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).
AstraZeneca in immunotherapy
Immunotherapy is a therapeutic approach designed to stimulate the
body's immune system to attack tumours. The Company's
Immuno-Oncology (IO) portfolio is anchored in immunotherapies that
have been designed to overcome anti-tumour immune suppression.
AstraZeneca is invested in using IO approaches that deliver
long-term survival for new groups of patients across tumour
types.
The Company is pursuing a comprehensive clinical-trial programme
that includes Imfinzi as a single treatment and in combination
with tremelimumab and other novel antibodies in multiple tumour
types, stages of disease, and lines of treatment, and where
relevant using the PD-L1 biomarker as a decision-making tool to
define the best potential treatment path for a
patient.
In addition, the ability to combine the IO portfolio with
radiation, chemotherapy, targeted small molecules from across
AstraZeneca's oncology pipeline, and from research partners, may
provide new treatment options across a broad range of
tumours.
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. Marcano-Bonilla
L, et
al. Biliary tract cancers:
epidemiology, molecular pathogenesis and genetic risk
associations. CCO. 2016;5(5).
2. ESMO. What is
Biliary Tract Cancer. Available here.
Accessed October 2021.
3. Siegel RL, Cancer statistics,
2020. CA Cancer J
Clin 2020;70:7-30.
4. ECIS - European
Cancer Information System. Available here.
Accessed October 2021.
5. Kohei
Nakachi, et al. Hepatobiliary and Pancreatic Oncology Group
of the Japan Clinical Oncology Group, A randomized Phase III trial
of adjuvant S-1 therapy vs. observation alone in resected biliary
tract cancer: Japan Clinical Oncology Group Study (JCOG1202,
ASCOT), Japanese Journal of Clinical
Oncology. 2018,48:392-395.
6. GBD 2017 Disease and Injury
Incidence and Prevalence Collaborators. Global, regional, and
national incidence, prevalence, and years lived with disability for
354 diseases and injuries for 195 countries and territories,
1990-2017: a systematic analysis for the Global Burden of Disease
Study 2017. Lancet. 2018;392(10159):1789-1858.
7. Turkes
F, et
al. Contemporary Tailored
Oncology Treatment of Biliary Tract
Cancers. Gastroenterol Res
Pract.
2019;2019:7698786.
8. Banales JM, Cardinale V, Carpino
G, et
al. Cholangiocarcinoma:
current knowledge and future perspectives consensus statement from
European network for the study of cholangiocarcinoma
(ENS-CCA). Nat Rev Gastroenterol
Hepatol.
2016;13:261-280.
9. Kirstein MM, Vogel A. Epidemiology
and risk factors of cholangiocarcinoma. Visc Med. 2016;32:395-400.
10. Khan SA, Tavolari S, Brandi G.
Cholangiocarcinoma: epidemiology and risk
factors. Liver
International. 2019;39(Suppl.1):19-31.
11. Bridgewater JA, Goodman KA, Kalyan
A, et
al. Biliary tract cancer:
epidemiology, radiotherapy, and molecular
profiling.
Am Soc Clin Oncol Educ Book.
2016;35:194-203.
12. Torre LA, Siegel RL, Islami
F, et
al. Worldwide burden of
and trends in mortality from gallbladder and other biliary tract
cancers. Clin Gastroenterol
Hepatol.
2018;16:427-437.
13. Banales JM, et al. Cholangiocarcinoma 2020: the next horizon in
mechanisms and management. Nature Reviews
Gastroenterology & Hepatology. 2020; 17: 557-588.
14. He XD, et al. Association of metabolic syndromes and risk
factors with ampullary tumors development: A case-control study in
China. World J
Gastroenterol. 2014; 20(28):
9541-9548.
15. WHO. World Cancer Fact
Sheet. Available here.
Accessed October 2021.
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:
25 October 2021
|
By: /s/
Adrian Kemp
|
|
Name:
Adrian Kemp
|
|
Title:
Company Secretary
|