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 January 2022
Commission
File Number: 001-11960
AstraZeneca PLC
1
Francis Crick Avenue
Cambridge
Biomedical Campus
Cambridge
CB2 0AA
United
Kingdom
Indicate
by check mark whether the registrant files or will file annual
reports under cover of Form 20-F or Form 40-F.
Form
20-F X Form 40-F __
Indicate
by check mark if the registrant is submitting the Form 6-K in paper
as permitted by Regulation S-T Rule 101(b)(1):
Indicate
by check mark if the registrant is submitting the Form 6-K in paper
as permitted by Regulation S-T Rule 101(b)(7): ______
Indicate
by check mark whether the registrant by furnishing the information
contained in this Form is also thereby furnishing the information
to the Commission pursuant to Rule 12g3-2(b) under the Securities
Exchange Act of 1934.
Yes __
No X
If
“Yes” is marked, indicate below the file number
assigned to the Registrant in connection with Rule 12g3-2(b):
82-_____________
AstraZeneca PLC
INDEX
TO EXHIBITS
1.
Imfinzi
improves survival in biliary tract cancer
19 January 2022 07:05 GMT
Imfinzi plus
chemotherapy reduced risk of death by 20% in 1st-line advanced
biliary tract cancer
TOPAZ-1 is the first Phase III trial to show improved
survival
with an immunotherapy combination in this setting
Combination did not increase discontinuations due to adverse events
vs. chemotherapy alone
Positive results from the TOPAZ-1 Phase III trial showed
AstraZeneca's Imfinzi (durvalumab), in combination with
standard-of-care chemotherapy, demonstrated a statistically
significant and clinically meaningful improvement in overall
survival (OS) and progression-free survival (PFS) versus
chemotherapy alone as a 1st-line treatment for patients with
advanced biliary tract cancer (BTC).
These results will be presented on 21 January at the 2022 American
Society of Clinical Oncology (ASCO) Gastrointestinal Cancers
Symposium.
BTC is a group of rare and aggressive cancers that occur in the
bile ducts and gallbladder.1,2 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 5% to 15% of all
patients with BTC surviving five years.6
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: "After
minimal progress for more than a decade in advanced biliary tract
cancer, the TOPAZ-1 results are a tremendous advance for our
patients, showing a clear survival benefit
for Imfinzi added to chemotherapy compared to standard
of care with a remarkable safety profile. This combination will
provide a desperately needed and potentially practice-changing new
treatment option in a setting where the current prognosis is
devastating."
Susan Galbraith, Executive Vice President, Oncology R&D,
AstraZeneca, said: "The results from the TOPAZ-1 trial challenge
treatment expectations in advanced biliary tract cancer and provide
compelling evidence that longer-term survival is possible. Overall
survival improves over time with an estimated one in four patients
on Imfinzi plus chemotherapy alive at two years
compared to one in ten on chemotherapy alone. This is a
potential new standard of care for patients in this setting and we
remain committed to making advances in gastrointestinal cancers
with high unmet need."
In a predefined interim analysis, patients treated
with Imfinzi in combination with standard-of-care
chemotherapy experienced a 20% reduction in the risk of death
versus chemotherapy alone (based on a hazard ratio [HR] of 0.80;
95% confidence interval [CI], 0.66-0.97; 2-sided p=0.021). Median
OS was 12.8 months versus 11.5 for chemotherapy. An
estimated 25% of patients were still alive at two years versus
10% for chemotherapy.
Results also showed a 25% reduction in the risk of disease
progression or death with Imfinzi plus chemotherapy (HR, 0.75; 95% CI,
0.64-0.89; 2-sided p=0.001). Median PFS was 7.2 months for the
combination versus 5.7 for chemotherapy. Patients treated
with Imfinzi plus chemotherapy achieved an objective
response rate (ORR) of 26.7% versus an ORR of 18.7% for patients
treated with chemotherapy alone.
Summary of efficacy
resultsi:
|
Imfinzi +
chemotherapy
(n=341)
|
Placebo + chemotherapy
(n=344)
|
OSii,iii
|
|
|
Percentage of patients with event
|
58.1
|
65.7
|
Median OS (95% CI) (in months)
|
12.8 (11.1, 14.0)
|
11.5 (10.1, 12.5)
|
HR (95% CI)
2-sided p-value
|
0.80 (0.66, 0.97)
0.021
|
OS rate at 18 months (95% CI) (%)
|
35.1 (29.1, 41.2)
|
25.6 (19.9, 31.7)
|
OS rate at 24 months (95% CI) (%)
|
24.9 (17.9, 32.5)
|
10.4 (4.7, 18.8)
|
PFSiv,v
|
|
|
Percentage of patients with event
|
80.9
|
86.3
|
Median PFS (95% CI) (in months)
|
7.2 (6.7, 7.4)
|
5.7 (5.6, 6.7)
|
HR (95% CI)
2-sided p-value
|
0.75 (0.64, 0.89)
0.001
|
ORR (%)
|
26.7
|
18.7
|
i.
Analysis was done at 62% maturity in OS data.
ii.
Investigator-assessed OS data cut-off date was 11 August
2021.
iii. Median
follow-up in censored patients at DCO: 13.7 months (range 0.4-27.2)
for Imfinzi plus chemotherapy, 12.6 months (range
0.7-26.0) for chemotherapy alone.
iv.
Investigator-assessed PFS data cut-off date was 11 August
2021.
v.
Median follow-up in censored patients at DCO: 9.2 months (range
0.0-24.0) for Imfinzi plus chemotherapy, 6.9 months (range
0.0-20.4) for chemotherapy alone.
Imfinzi plus chemotherapy
did not increase the discontinuation rate due to adverse events
(AEs) compared to chemotherapy alone. Grade 3 or 4
treatment-related AEs were experienced by 62.7% of patients treated
with Imfinzi and chemotherapy, and by 64.9% of patients
receiving chemotherapy alone. Treatment-related AEs led to
discontinuation in 8.9% of patients treated with
the Imfinzi combination versus 11.4% of patients
receiving chemotherapy.
In December 2020, Imfinzi was granted Orphan Drug Designation in the
US for the treatment of BTC. In October
2021, an Independent Data
Monitoring Committee recommended the TOPAZ-1 Phase III trial to be
unblinded at an interim analysis due to clear evidence of efficacy
for Imfinzi plus chemotherapy.
An additional presentation featured during the
ASCO Gastrointestinal Cancers Symposium will
showcase Imfinzi data from the HIMALAYA Phase III
trial, demonstrating the potential of this medicine in the
treatment of unresectable liver
cancer.
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.1,6 Gallbladder
cancer is more common in certain regions of South America, India
and Japan.7
Apart from ampullary cancer, early-stage BTC often presents without
clear symptoms and most new cases of BTC are therefore diagnosed at
an advanced stage, when treatment options are limited and the
prognosis is poor.8-10
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 primary endpoint was OS and key secondary endpoints included
progression-free survival, objective response rate and safety. The
trial was conducted in 105 centres across 17 countries including in
the US, Europe, South America and several countries in Asia
including South Korea, Thailand, Japan and China.
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
small cell lung cancer, NSCLC, bladder cancer, several GI cancers,
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.11
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.
The Company aims to understand the potential
of Enhertu (trastuzumab deruxtecan), a HER2-directed
antibody drug conjugate, in colorectal and gastric cancers - the
two most common GI 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, and 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 at:
https://www.esmo.org/content/download/266801/5310983/1/EN-Biliary-Tract-Cancer-Guide-for-Patients.pdf.
Accessed January 2022.
3. Siegel R, et al. Cancer Statistics. CA Cancer J
Clin. 2020; 70:
7-30.
4. Nakachi K, et al. A randomized Phase III trial of adjuvant S1
therapy vs. observation alone in resected biliary tract cancer:
Japan Clinical Oncology Group Study (JCOG1202,
ASCOT). Japanese Journal of Clinical
Oncology. 2018; 48(4):
392-395.
5. 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.
6. Turkes F, et al. Contemporary Tailored Oncology Treatment of
Biliary Tract Cancers. Gastroenterol Res
Pract. 2019;
2019:7698786.
7. Rawla P, et al. Epidemiology of gallbladder
cancer. Clin Exp
Hepatol. 2019; 5(2):
93-102.
8. Banales JM, et al. Cholangiocarcinoma 2020: the next horizon in
mechanisms and management. Nature Reviews
Gastroenterology & Hepatology. 2020; 17: 557-588.
9. Mehrotra B. Gallbladder cancer: Epidemiology, risk factors,
clinical features, and diagnosis. Available at:
https://www.uptodate.com/contents/gallbladder-cancer-epidemiology-risk-factors-clinical-features-and-diagnosis.
Accessed January 2022.
10. 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.
11. WHO. World Cancer Fact Sheet. Available at: https://gco.iarc.fr/today/data/factsheets/populations/900-world-fact-sheets.pdf.
Accessed January 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:
19 January 2022
|
By: /s/
Adrian Kemp
|
|
Name:
Adrian Kemp
|
|
Title:
Company Secretary
|
AstraZeneca (NASDAQ:AZN)
Historical Stock Chart
From Feb 2024 to Mar 2024
AstraZeneca (NASDAQ:AZN)
Historical Stock Chart
From Mar 2023 to Mar 2024