<SEC-DOCUMENT>0001654954-21-011113.txt : 20211015
<SEC-HEADER>0001654954-21-011113.hdr.sgml : 20211015
<ACCEPTANCE-DATETIME>20211015071305
ACCESSION NUMBER:		0001654954-21-011113
CONFORMED SUBMISSION TYPE:	6-K
PUBLIC DOCUMENT COUNT:		1
CONFORMED PERIOD OF REPORT:	20211015
FILED AS OF DATE:		20211015
DATE AS OF CHANGE:		20211015

FILER:

	COMPANY DATA:	
		COMPANY CONFORMED NAME:			ASTRAZENECA PLC
		CENTRAL INDEX KEY:			0000901832
		STANDARD INDUSTRIAL CLASSIFICATION:	PHARMACEUTICAL PREPARATIONS [2834]
		IRS NUMBER:				000000000
		STATE OF INCORPORATION:			X0
		FISCAL YEAR END:			1231

	FILING VALUES:
		FORM TYPE:		6-K
		SEC ACT:		1934 Act
		SEC FILE NUMBER:	001-11960
		FILM NUMBER:		211324781

	BUSINESS ADDRESS:	
		STREET 1:		1 FRANCIS CRICK AVENUE
		STREET 2:		CAMBRIDGE BIOMEDICAL CAMPUS
		CITY:			CAMBRIDGE
		STATE:			X0
		ZIP:			CB2 0AA
		BUSINESS PHONE:		011 44 20 7304 5000

	MAIL ADDRESS:	
		STREET 1:		1 FRANCIS CRICK AVENUE
		STREET 2:		CAMBRIDGE BIOMEDICAL CAMPUS
		CITY:			CAMBRIDGE
		STATE:			X0
		ZIP:			CB2 0AA

	FORMER COMPANY:	
		FORMER CONFORMED NAME:	ZENECA GROUP PLC
		DATE OF NAME CHANGE:	19930422
</SEC-HEADER>
<DOCUMENT>
<TYPE>6-K
<SEQUENCE>1
<FILENAME>a2140p.htm
<DESCRIPTION>IMFINZI & TREMELIMUMAB IMPROVED OS IN LIVER CANCER
<TEXT>
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PLC</font></div>
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<font style="font-family: Times New Roman; font-size: 13px">INDEX
TO EXHIBITS</font></div>
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<font style="font-size: 13px; font-family: Times New Roman">1.</font></div>
<div style="text-align: justify; display: table-cell"><font style="font-family: Times New Roman; font-size: 13px">Imfinzi &amp;
tremelimumab improved OS in liver cancer</font></div>
</div>
</div>
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<font style="font-family: Times New Roman; font-size: 13px">&#xA0;</font></div>
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<font style="font-family: Times New Roman; font-size: 13px">&#xA0;</font></div>
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<font style="font-family: Times New Roman; font-size: 13px">&#xA0;</font></div>
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<font style="color: #000000; font-family: Times New Roman; font-size: 13px">
15 October 2021 7:00 BST</font></div>
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&#xA0;</font></div>
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<font style="font-weight: bold; font-family: Times New Roman; font-size: 13px">
<font style="font-style: italic; color: #000000">Imfinzi</font><font style="color: #000000">&#xA0;plus tremelimumab significantly improved
overall survival in HIMALAYA Phase III trial in 1st-line
unresectable liver cancer</font></font></div>
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<font style="font-weight: bold; color: #000000; font-family: Times New Roman; font-size: 13px">
&#xA0;</font></div>
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<font style="font-weight: bold; font-style: italic; color: #000000; font-family: Times New Roman; font-size: 13px">
Trial met primary endpoint of overall survival with a single
priming</font></div>
<div style="text-align: center; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="color: #000000; font-weight: bold; font-style: italic; font-family: Times New Roman; font-size: 13px">
dose of tremelimumab plus Imfinzi every four weeks vs.
sorafenib</font></div>
<div style="text-align: left; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-weight: bold; font-style: italic; color: #000000; font-family: Times New Roman; font-size: 13px">
&#xA0;</font></div>
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<font style="font-weight: bold; font-style: italic; color: #000000; font-family: Times New Roman; font-size: 13px">
Imfinzi monotherapy met the overall survival endpoint of
non-inferiority vs. sorafenib</font></div>
<div style="text-align: center; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="color: #000000; font-family: Times New Roman; font-size: 13px">
&#xA0;</font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-family: Times New Roman; font-size: 13px"><font style="color: #000000">
Positive high-level results from the HIMALAYA Phase III trial
showed a single, high priming dose of tremelimumab added
to&#xA0;</font><font style="font-style: italic; color: #000000">Imfinzi</font><font style="color: #000000">&#xA0;(durvalumab) demonstrated a statistically
significant and clinically meaningful overall survival (OS) benefit
versus sorafenib as a 1st-line treatment for patients
with&#xA0;unresectable&#xA0;hepatocellular carcinoma
(HCC)</font><font style="color: #000000; font-family: Times New Roman">&#xA0;</font><font style="color: #000000">who
had not received prior systemic therapy and were not eligible for
localised treatment.&#xA0;This novel dose and schedule of
tremelimumab, an anti-CTLA4 antibody, and&#xA0;</font><font style="font-style: italic; color: #000000">Imfinzi</font><font style="color: #000000">&#xA0;is called the STRIDE regimen (Single
Tremelimumab Regular Interval Durvalumab). The combination
demonstrated a favourable safety profile, and the addition of
tremelimumab to&#xA0;</font><font style="font-style: italic; color: #000000">Imfinzi</font><font style="color: #000000">&#xA0;did not increase severe hepatic
toxicity.</font></font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="color: #000000; font-family: Times New Roman; font-size: 13px">
&#xA0;</font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-family: Times New Roman; font-size: 13px"><font style="font-style: italic; color: #000000">
Imfinzi&#xA0;</font><font style="color: #000000">alone demonstrated
non-inferior OS to sorafenib with a numerical trend in favour
of&#xA0;</font><font style="font-style: italic; color: #000000">Imfinzi</font><font style="color: #000000">&#xA0;and an improved tolerability profile
compared to sorafenib.</font></font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="color: #000000; font-family: Times New Roman; font-size: 13px">
&#xA0;</font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-family: Times New Roman; font-size: 13px"><font style="color: #000000">
Liver cancer, of which HCC is the most common type,&#xA0;is the
third leading cause of cancer death and the sixth most commonly
diagnosed cancer worldwide with approximately 900,000 people
diagnosed each year.</font><font style="font-size: 70%; vertical-align: top; color: #000000">1-2</font><font style="color: #000000">&#xA0;Only
7% of patients with advanced disease survive five
years.</font><font style="font-size: 70%; vertical-align: top; color: #000000">3</font></font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="color: #000000; font-family: Times New Roman; font-size: 13px">
&#xA0;</font></div>
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<font style="color: #000000; font-family: Times New Roman; font-size: 13px">
Ghassan Abou-Alfa, MD, MBA, Attending Physician at Memorial Sloan
Kettering Cancer Center and principal investigator in the HIMALAYA
Phase III trial, said:&#xA0;"HIMALAYA is the first Phase III trial
to add a novel single priming dose of an anti-CTLA4 antibody to
another checkpoint inhibitor, durvalumab. This serves to boost the
patient's own immune system against their liver cancer, aiming to
maximise long-term survival with minimal side effects. This is very
exciting news for our patients."</font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="color: #000000; font-family: Times New Roman; font-size: 13px">
&#xA0;</font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="color: #000000; font-family: Times New Roman; font-size: 13px">
Susan Galbraith, Executive Vice President, Oncology R&amp;D,
AstraZeneca, said: "Inhibition of CTLA-4 has shown the ability to
drive benefit particularly in the tail of the survival curve in
several settings. This is the first time a dual immunotherapy
regimen has improved overall survival as a 1st-line treatment for
patients with unresectable liver cancer for whom treatment options
are limited and long-term outcomes are poor."</font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="color: #000000; font-family: Times New Roman; font-size: 13px">
&#xA0;</font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="color: #000000; font-family: Times New Roman; font-size: 13px">
The data from the HIMALAYA Phase III trial will be presented at a
forthcoming medical meeting.</font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="color: #000000; font-family: Times New Roman; font-size: 13px">
&#xA0;</font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-family: Times New Roman; font-size: 13px"><font style="font-style: italic; color: #000000">
Imfinzi</font><font style="color: #000000">&#xA0;and tremelimumab
were granted Orphan Drug Designations in the US for the treatment
of HCC in 2020. Tremelimumab was also granted orphan designation in
the EU in HCC in 2020.</font></font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-weight: bold; color: #000000; font-family: Times New Roman; font-size: 13px">
&#xA0;</font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="text-decoration: underline; color: #000000; font-weight: bold; font-family: Times New Roman; font-size: 13px">
Notes</font></div>
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<font style="font-weight: bold; color: #000000; font-family: Times New Roman; font-size: 13px">
&#xA0;</font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-weight: bold; color: #000000; font-family: Times New Roman; font-size: 13px">
Liver cancer</font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-family: Times New Roman; font-size: 13px"><font style="color: #000000">
About 75% of all primary liver cancers are HCC.</font><font style="font-size: 70%; vertical-align: top; color: #000000">1</font><font style="color: #000000">&#xA0;Between
80-90% of all patients with HCC also have cirrhosis, which is
primarily caused by infection with the hepatitis B or C
viruses.</font><font style="font-size: 70%; vertical-align: top; color: #000000">4</font><font style="color: #000000">&#xA0;Chronic
liver diseases are associated with inflammation that, over time,
results in immunosuppression and can lead to the development of
HCC.</font><font style="font-size: 70%; vertical-align: top; color: #000000">4,5</font></font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="color: #000000; font-family: Times New Roman; font-size: 13px">
&#xA0;</font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-family: Times New Roman; font-size: 13px"><font style="color: #000000">
The unique immune environment of liver cancer provides clear
rationale for researching medicines that harness the power of the
immune system to treat HCC.</font><font style="font-size: 70%; vertical-align: top; color: #000000">6</font><font style="color: #000000">&#xA0;A
critical unmet need exists for patients with HCC who face limited
treatment options.</font><font style="font-size: 70%; vertical-align: top; color: #000000">6</font><font style="color: #000000">&#xA0;More
than half of patients are diagnosed at advanced stages of the
disease, often when symptoms first appear.</font><font style="font-size: 70%; vertical-align: top; color: #000000">6</font></font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="color: #000000; font-family: Times New Roman; font-size: 13px">
&#xA0;</font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-weight: bold; color: #000000; font-family: Times New Roman; font-size: 13px">
HIMALAYA</font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-family: Times New Roman; font-size: 13px"><font style="color: #000000">
HIMALAYA was a randomised, open-label, multicentre, global Phase
III trial of&#xA0;</font><font style="font-style: italic; color: #000000">Imfinzi</font><font style="color: #000000">&#xA0;monotherapy and the STRIDE regimen,
comprising&#xA0;a single priming dose of tremelimumab 300mg added
to&#xA0;</font><font style="font-style: italic; color: #000000">Imfinzi</font><font style="color: #000000">&#xA0;1500mg followed by&#xA0;</font><font style="font-style: italic; color: #000000">Imfinzi</font><font style="color: #000000">&#xA0;every four weeks&#xA0;versus sorafenib, a
standard-of-care multi-kinase inhibitor, in a total of 1,324
patients with unresectable, advanced HCC who had not been treated
with prior systemic therapy and were not eligible for locoregional
therapy (treatment localised to the liver and surrounding
tissue).</font></font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="color: #000000; font-family: Times New Roman; font-size: 13px">
&#xA0;</font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-family: Times New Roman; font-size: 13px"><font style="color: #000000">
The trial was conducted in 190 centres across 16 countries,
including in the US, Canada, Europe, South America and Asia. The
primary endpoint was OS for STRIDE versus sorafenib and key
secondary endpoints included OS for&#xA0;</font><font style="font-style: italic; color: #000000">Imfinzi</font><font style="color: #000000">&#xA0;versus sorafenib, objective response rate
and progression-free survival (PFS) for STRIDE and
for&#xA0;</font><font style="font-style: italic; color: #000000">Imfinzi</font><font style="color: #000000">&#xA0;alone.</font></font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="color: #000000; font-family: Times New Roman; font-size: 13px">
&#xA0;</font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-weight: bold; font-style: italic; color: #000000; font-family: Times New Roman; font-size: 13px">
Imfinzi</font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-family: Times New Roman; font-size: 13px"><font style="font-style: italic; color: #000000">
Imfinzi</font><font style="color: #000000">&#xA0;(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.</font></font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="color: #000000; font-family: Times New Roman; font-size: 13px">
&#xA0;</font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-family: Times New Roman; font-size: 13px"><font style="font-style: italic; color: #000000">
Imfinzi</font><font style="color: #000000">&#xA0;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.</font></font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="color: #000000; font-family: Times New Roman; font-size: 13px">
&#xA0;</font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-family: Times New Roman; font-size: 13px"><font style="font-style: italic; color: #000000">
Imfinzi</font><font style="color: #000000">&#xA0;is also approved
in the US, EU, Japan, China and many other countries around the
world for the treatment of&#xA0;extensive-stage small cell lung
cancer&#xA0;(ES-SCLC) based on the CASPIAN Phase III
trial.</font></font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="color: #000000; font-family: Times New Roman; font-size: 13px">
&#xA0;</font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-family: Times New Roman; font-size: 13px"><font style="font-style: italic; color: #000000">
Imfinzi</font><font style="color: #000000">&#xA0;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&#xA0;</font><font style="font-style: italic; color: #000000">Imfinzi</font><font style="color: #000000">.</font></font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="color: #000000; font-family: Times New Roman; font-size: 13px">
&#xA0;</font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-family: Times New Roman; font-size: 13px"><font style="color: #000000">
In 1st-line Stage IV NSCLC, positive results from the POSEIDON
Phase III trial showed&#xA0;</font><font style="font-style: italic; color: #000000">Imfinzi</font><font style="color: #000000">&#xA0;plus chemotherapy with a short course of
tremelimumab 75mg demonstrated a statistically significant and
clinically meaningful improvement in OS and PFS compared to
chemotherapy.</font></font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="color: #000000; font-family: Times New Roman; font-size: 13px">
&#xA0;</font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-family: Times New Roman; font-size: 13px"><font style="color: #000000">
As part of a broad development programme,&#xA0;</font><font style="font-style: italic; color: #000000">Imfinzi</font><font style="color: #000000">&#xA0;is being tested as a single treatment and in
combinations with other anti-cancer treatments for patients with
NSCLC, SCLC, bladder cancer, HCC, biliary tract cancer (BTC),
oesophageal cancer, gastric and gastroesophageal cancer, cervical
cancer, ovarian cancer, endometrial cancer, and other solid
tumours.</font></font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="color: #000000; font-family: Times New Roman; font-size: 13px">
&#xA0;</font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-weight: bold; color: #000000; font-family: Times New Roman; font-size: 13px">
Tremelimumab</font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="color: #000000; font-family: Times New Roman; font-size: 13px">
Tremelimumab is a human monoclonal antibody and potential new
medicine that targets the activity of cytotoxic
T-lymphocyte-associated protein 4 (CTLA-4). Tremelimumab blocks the
activity of CTLA-4, contributing to T-cell activation, priming the
immune response to cancer and fostering cancer cell
death.</font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="color: #000000; font-family: Times New Roman; font-size: 13px">
&#xA0;</font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-family: Times New Roman; font-size: 13px"><font style="color: #000000">
Tremelimumab is being tested in a clinical trial programme in
combination with&#xA0;</font><font style="font-style: italic; color: #000000">Imfinzi</font><font style="color: #000000">&#xA0;in NSCLC, SCLC, bladder cancer and liver
cancer.</font></font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-weight: bold; color: #000000; font-family: Times New Roman; font-size: 13px">
&#xA0;</font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-weight: bold; color: #000000; font-family: Times New Roman; font-size: 13px">
AstraZeneca in gastrointestinal cancers</font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-family: Times New Roman; font-size: 13px"><font style="color: #000000">
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 2020, GI cancers
collectively represented approximately 5.1 million new diagnoses
leading to approximately 3.6 million deaths.</font><font style="font-size: 70%; vertical-align: top; color: #000000">7</font></font></div>
<div><font style="font-family: Times New Roman; font-size: 10">&#xA0;</font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="color: #000000; font-family: Times New Roman; font-size: 13px">
Within this programme, the Company is committed to improving
outcomes in gastric, liver, biliary tract, oesophageal, pancreatic,
and colorectal cancers.</font></div>
<div><font style="font-family: Times New Roman; font-size: 10">&#xA0;</font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-family: Times New Roman; font-size: 13px"><font style="font-style: italic; color: #000000">
Imfinzi&#xA0;</font><font style="color: #000000">(durvalumab) is
being assessed in combinations including with tremelimumab in HCC,
BTC, oesophageal and gastric cancers in an extensive development
programme spanning early to late-stage disease across
settings.</font></font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="color: #000000; font-family: Times New Roman; font-size: 13px">
&#xA0;</font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-family: Times New Roman; font-size: 13px"><font style="color: #000000">
The Company aims to understand the potential
of&#xA0;</font><font style="font-style: italic; color: #000000">Enhertu</font><font style="color: #000000">&#xA0;(trastuzumab deruxtecan), a HER2-directed
antibody drug conjugate,</font><font style="font-style: italic; color: #000000">&#xA0;</font><font style="color: #000000">in the two most common GI cancers, colorectal and
gastric cancers.</font><font style="font-size: 70%; vertical-align: top; color: #000000">2</font><font style="color: #000000">&#xA0;</font><font style="font-style: italic; color: #000000">Enhertu</font><font style="color: #000000">&#xA0;is
jointly developed and commercialised by AstraZeneca and Daiichi
Sankyo.</font></font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="color: #000000; font-family: Times New Roman; font-size: 13px">
&#xA0;</font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-family: Times New Roman; font-size: 13px"><font style="font-style: italic; color: #000000">
Lynparza&#xA0;</font><font style="color: #000000">(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.&#xA0;</font><font style="font-style: italic; color: #000000">Lynparza</font><font style="color: #000000">&#xA0;is developed and commercialised in
collaboration with MSD (Merck &amp; Co., Inc. inside the US and
Canada).</font></font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="color: #000000; font-family: Times New Roman; font-size: 13px">
&#xA0;</font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-weight: bold; color: #000000; font-family: Times New Roman; font-size: 13px">
AstraZeneca in immunotherapy</font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="color: #000000; font-family: Times New Roman; font-size: 13px">
Immunotherapy is a therapeutic approach designed to stimulate the
body's immune system to attack tumours. The
Company's&#xA0;Immuno-Oncology (IO)&#xA0;portfolio is anchored in
immunotherapies that have been designed to overcome anti-tumour
immune suppression.</font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="color: #000000; font-family: Times New Roman; font-size: 13px">
&#xA0;</font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="color: #000000; font-family: Times New Roman; font-size: 13px">
AstraZeneca is invested in using IO approaches that deliver
long-term survival for new groups of patients across tumour
types.</font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="color: #000000; font-family: Times New Roman; font-size: 13px">
&#xA0;</font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-family: Times New Roman; font-size: 13px"><font style="color: #000000">
The Company is pursuing a comprehensive clinical trial programme
that includes&#xA0;</font><font style="font-style: italic; color: #000000">Imfinzi</font><font style="color: #000000">&#xA0;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.</font></font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="color: #000000; font-family: Times New Roman; font-size: 13px">
&#xA0;</font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="color: #000000; font-family: Times New Roman; font-size: 13px">
In addition, the ability to combine the IO portfolio with
radiation, chemotherapy, small, targeted molecules from across
AstraZeneca's oncology pipeline, and from research partners, may
provide new treatment options across a broad range of
tumours.</font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="color: #000000; font-family: Times New Roman; font-size: 13px">
&#xA0;</font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-weight: bold; color: #000000; font-family: Times New Roman; font-size: 13px">
AstraZeneca in oncology</font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="color: #000000; font-family: Times New Roman; font-size: 13px">
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.</font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="color: #000000; font-family: Times New Roman; font-size: 13px">
&#xA0;</font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="color: #000000; font-family: Times New Roman; font-size: 13px">
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.</font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="color: #000000; font-family: Times New Roman; font-size: 13px">
&#xA0;</font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="color: #000000; font-family: Times New Roman; font-size: 13px">
AstraZeneca has the vision to redefine cancer care and, one day,
eliminate cancer as a cause of death.</font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="color: #000000; font-family: Times New Roman; font-size: 13px">
&#xA0;</font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-weight: bold; color: #000000; font-family: Times New Roman; font-size: 13px">
AstraZeneca</font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-family: Times New Roman; font-size: 13px"><font style="color: #000000">
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 &amp; Metabolism, and Respiratory &amp;
Immunology. Based in Cambridge, UK, AstraZeneca operates in over
100 countries and its innovative medicines are used by millions of
patients worldwide. Please visit&#xA0;</font><font style="text-decoration: underline; color: #0000FF">astrazeneca.com</font><font style="color: #000000">&#xA0;and
follow the Company on Twitter&#xA0;</font><font style="text-decoration: underline; color: #0000FF">@AstraZeneca</font><font style="color: #000000">.</font></font></div>
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<font style="font-weight: bold; color: #000000; font-family: Times New Roman; font-size: 13px">
Contacts</font></div>
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<font style="font-family: Times New Roman; font-size: 13px"><font style="color: #000000">
For details on how to contact the Investor Relations Team, please
click&#xA0;</font><font style="text-decoration: underline; color: #0000FF">here</font><font style="color: #000000">.
For Media contacts, click&#xA0;</font><font style="text-decoration: underline; color: #0000FF">here</font><font style="color: #000000">.</font></font></div>
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References</font></div>
<div style="margin-left: 0px; display: table;">
<div style="display: table-row">
<div style="text-align: left; display: table-cell; width: 24px">
<font style="color: #000000; font-family: Times New Roman; font-size: 13px">1.</font></div>
<div style="text-align: justify; display: table-cell"><font style="font-family: Times New Roman; font-size: 13px"><font style="color: #000000; font-size: 13px">ASCO. Liver Cancer: View All
Pages. Available at:&#xA0;</font><font style="text-decoration: underline; color: #0000FF; font-size: 13px">https://www.cancer.net/cancer-types/liver-cancer/view-all</font><font style="color: #000000; font-size: 13px">.
Accessed October 2021.</font></font></div>
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<div style="text-align: left; display: table-cell; width: 24px">
<font style="color: #000000; font-family: Times New Roman; font-size: 13px">2.</font></div>
<div style="text-align: justify; display: table-cell"><font style="font-family: Times New Roman; font-size: 13px"><font style="color: #000000; font-size: 13px">WHO. Liver Cancer Fact Sheet.
Available at:&#xA0;</font><font style="text-decoration: underline; color: #0000FF; font-size: 13px">https://gco.iarc.fr/today/data/factsheets/cancers/11-Liver-fact-sheet.pdf</font><font style="color: #000000; font-size: 13px">.
Accessed October 2021.</font></font></div>
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<font style="color: #000000; font-size: 13px; font-family: Times New Roman">3.</font></div>
<div style="text-align: justify; display: table-cell"><font style="font-family: Times New Roman; font-size: 13px"><font style="color: #000000">Sayiner M, et al. Disease Burden of Hepatocellular
Carcinoma: A Global Perspective.&#xA0;</font><font style="font-style: italic; color: #000000">Digestive Diseases and
Sciences</font><font style="color: #000000">. 2019; 64:
910-917.&#x200B;</font></font></div>
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<font style="color: #000000; font-size: 13px; font-family: Times New Roman">4.</font></div>
<div style="text-align: justify; display: table-cell"><font style="font-family: Times New Roman; font-size: 13px"><font style="color: #000000">Tarao K, et al. Real impact of liver cirrhosis on
the development of hepatocellular carcinoma in various liver
diseases-meta</font><font style="color: #000000; font-family: Times New Roman">&#x2010;</font><font style="color: #000000">analytic
assessment.&#xA0;</font><font style="font-style: italic; color: #000000">Cancer Med</font><font style="color: #000000">. 2019; 8(3): 1054-1065.</font></font></div>
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<font style="color: #000000; font-size: 13px; font-family: Times New Roman">5.</font></div>
<div style="text-align: justify; display: table-cell"><font style="font-family: Times New Roman; font-size: 13px"><font style="color: #000000">Yu LX, et al. Role of nonresolving inflammation in
hepatocellular carcinoma development and
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<font style="color: #000000; font-size: 13px; font-family: Times New Roman">6.</font></div>
<div style="text-align: justify; display: table-cell"><font style="font-family: Times New Roman; font-size: 13px"><font style="color: #000000">Colagrande S, et al. Challenges of advanced
hepatocellular carcinoma.&#xA0;</font><font style="font-style: italic; color: #000000">World J
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7645-7659.</font></font></div>
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<font style="color: #000000; font-family: Times New Roman; font-size: 13px">7.</font></div>
<div style="text-align: justify; display: table-cell"><font style="font-family: Times New Roman; font-size: 13px"><font style="color: #000000; font-size: 13px">WHO. World Cancer Fact Sheet.
Available at:&#xA0;</font><font style="text-decoration: underline; color: #0000FF; font-size: 13px">https://gco.iarc.fr/today/data/factsheets/populations/900-world-fact-sheets.pdf</font><font style="color: #000000; font-size: 13px">.
Accessed October 2021.</font></font></div>
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</div>
<div style="text-align: left; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="color: #000000; font-family: Times New Roman; font-size: 13px">
&#xA0;</font></div>
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<font style="font-weight: bold; color: #000000; font-family: Times New Roman; font-size: 13px">
Adrian Kemp</font></div>
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<font style="font-weight: bold; color: #000000; font-family: Times New Roman; font-size: 13px">
Company Secretary</font></div>
<div style="text-align: left; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-weight: bold; color: #000000; font-family: Times New Roman; font-size: 13px">
AstraZeneca PLC</font></div>
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<font style="color: #000000; font-family: Times New Roman; font-size: 13px">
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<font style="text-decoration: underline; font-family: Times New Roman; font-size: 13px">
SIGNATURES</font></div>
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<font style="font-family: Times New Roman; font-size: 13px">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.</font></div>
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<font style="font-family: Times New Roman; font-size: 13px">AstraZeneca
PLC</font></div>
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<font style="font-family: Times New Roman; font-size: 13px">Date:
<font style="font-size: 13px">15 October 2021</font></font></div>
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<font style="font-family: Times New Roman; font-size: 13px">By: /s/
Adrian Kemp</font></div>
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<font style="font-family: Times New Roman; font-size: 13px">Name:
Adrian Kemp</font></div>
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<font style="font-family: Times New Roman; font-size: 13px">Title:
Company Secretary</font></div>
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