<SEC-DOCUMENT>0001654954-25-002412.txt : 20250307
<SEC-HEADER>0001654954-25-002412.hdr.sgml : 20250307
<ACCEPTANCE-DATETIME>20250307071702
ACCESSION NUMBER:		0001654954-25-002412
CONFORMED SUBMISSION TYPE:	6-K
PUBLIC DOCUMENT COUNT:		1
CONFORMED PERIOD OF REPORT:	20250307
FILED AS OF DATE:		20250307
DATE AS OF CHANGE:		20250307

FILER:

	COMPANY DATA:	
		COMPANY CONFORMED NAME:			ASTRAZENECA PLC
		CENTRAL INDEX KEY:			0000901832
		STANDARD INDUSTRIAL CLASSIFICATION:	PHARMACEUTICAL PREPARATIONS [2834]
		ORGANIZATION NAME:           	03 Life Sciences
		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:		25717557

	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>a8006z.htm
<DESCRIPTION>IMFINZI IMPROVED EFS IN EARLY-STAGE GASTRIC CANCER
<TEXT>
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AstraZeneca 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-weight: bold; font-style: italic; font-family: Times New Roman; font-size: 13px">
1.</font></div>
<div style="text-align: justify; display: table-cell"><font style="font-weight: bold; font-style: italic; font-family: Times New Roman; font-size: 13px">
Imfinzi improved EFS in early-stage gastric 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="color: #000000; font-family: Times New Roman; font-size: 13px">
7 March 2025</font></div>
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&#xA0;</font></div>
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<font style="font-family: Times New Roman; font-size: 16px"><font style="font-weight: bold; font-style: italic; color: #000000">
Imfinzi-</font><font style="font-weight: bold; color: #000000">based</font><font style="color: #000000; font-family: Times New Roman">&#xA0;</font><font style="font-weight: bold; color: #000000">regimen
demonstrated statistically significant and clinically meaningful
improvement in event-free survival in resectable early-stage
gastric and gastroesophageal junction cancers</font></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">
MATTERHORN is first global, randomised Phase III trial to
demonstrate superior event-free survival with an immunotherapy
combination over standard of care in this setting</font></div>
<div style="text-align: center; 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>
<div style="text-align: center; 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 plus chemotherapy more than doubled pathologic</font></div>
<div style="text-align: center; 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">
complete response rate in previously reported analysis of this
trial in 2023</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 MATTERHORN Phase III trial
showed perioperative treatment with
AstraZeneca's&#xA0;</font><font style="font-style: italic; color: #000000">Imfinzi</font><font style="color: #000000">&#xA0;(durvalumab) in combination with
standard-of-care FLOT (fluorouracil, leucovorin, oxaliplatin, and
docetaxel) chemotherapy demonstrated a statistically significant
and clinically meaningful improvement in the primary endpoint of
event-free survival (EFS). Patients were treated with
neoadjuvant&#xA0;</font><font style="font-style: italic; color: #000000">Imfinzi</font><font style="color: #000000">&#xA0;in combination with
chemotherapy</font><font style="color: #000000; font-family: Times New Roman">&#xA0;</font><font style="color: #000000">before
surgery, followed by adjuvant&#xA0;</font><font style="font-style: italic; color: #000000">Imfinzi</font><font style="color: #000000">&#xA0;in combination with chemotherapy,
then&#xA0;</font><font style="font-style: italic; color: #000000">Imfinzi</font><font style="color: #000000">&#xA0;monotherapy. The trial evaluated this
regimen versus perioperative chemotherapy alone for patients with
resectable, early-stage and locally advanced (Stages II, III, IVA)
gastric and gastroesophageal junction (GEJ)
cancers.</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">
For the secondary endpoint of overall survival (OS), a strong trend
was observed in favour of the&#xA0;</font><font style="font-style: italic; color: #000000">Imfinzi-</font><font style="color: #000000">based regimen at this interim analysis. The trial
will continue to follow OS, which will be formally assessed at the
final analysis.</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">
Gastric cancer is the fifth leading cause of cancer death globally,
with nearly one million people diagnosed each
year.</font><font style="font-size: 70%; vertical-align: top; color: #000000">1</font><font style="color: #000000">&#xA0;In
2024, there were roughly 43,000 drug-treated patients in the US,
European Union (EU) and Japan in early-stage and locally advanced
gastric or GEJ cancer.</font><font style="font-size: 70%; vertical-align: top; color: #000000">2</font><font style="color: #000000">&#xA0;Approximately
62,000 patients in these regions are expected to be newly diagnosed
in this setting by 2030.</font><font style="font-size: 70%; vertical-align: top; color: #000000">3&#xA0;</font></font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-size: 70%; vertical-align: top; color: #000000; font-family: Times New Roman">
&#xA0;</font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: -1px; text-indent: 0px">
<font style="font-family: Times New Roman; font-size: 13px"><font style="color: #000000">Yelena Y Janjigian, MD, Chief Attending Physician
of the Gastrointestinal Medical Oncology Service, Memorial Sloan
Kettering Cancer Center, New York and principal investigator in the
trial, said:</font><font style="color: #000000; font-family: Times New Roman">&#xA0;</font><font style="color: #000000">"Despite
receiving curative-intent chemotherapy and surgery, patients with
gastric cancer commonly face disease recurrence and have a poor
prognosis. These exciting data from MATTERHORN show that a
durvalumab-based perioperative regimen resulted in
a</font><font style="color: #000000; font-family: Times New Roman">&#xA0;</font><font style="color: #000000">clinically
meaningful improvement in patient outcomes, including decreasing
the risk of the cancer coming back."</font></font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: -1px; 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: -1px; text-indent: 0px">
<font style="font-family: Times New Roman; font-size: 13px"><font style="color: #000000">Cristian Massacesi, Chief Medical Officer and
Oncology Chief Development Officer, AstraZeneca, said: "MATTERHORN
is the first Phase III trial of an immunotherapy to show a
statistically significant improvement in event-free survival in
patients with resectable gastric and gastroesophageal junction
cancers.</font><font style="color: #000000; font-family: Times New Roman">&#xA0;</font><font style="color: #000000">This
perioperative approach with&#xA0;</font><font style="font-style: italic; color: #000000">Imfinzi</font><font style="color: #000000">&#xA0;underscores our commitment to moving into
earlier stages of cancer where novel therapies can have the biggest
impact on patients' lives."</font></font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: -1px; 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 safety profile for&#xA0;</font><font style="font-style: italic; color: #000000">Imfinzi</font><font style="color: #000000">&#xA0;and FLOT chemotherapy was consistent with
the known profiles of each medicine, and there were no new safety
findings.</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 a</font><font style="color: #000000; font-family: Times New Roman">&#xA0;</font><font style="text-decoration: underline; color: #0000FF">previously
reported</font><font style="color: #000000; font-family: Times New Roman">&#xA0;</font><font style="color: #000000">interim
analysis for the key secondary endpoint of pathologic complete
response (pCR),</font><font style="color: #000000; font-family: Times New Roman">&#xA0;</font><font style="color: #000000">the&#xA0;</font><font style="font-style: italic; color: #000000">Imfinzi</font><font style="color: #000000">&#xA0;combination&#xA0;more
than doubled the pCR rate compared to neoadjuvant chemotherapy
alone (19% versus 7%, odds ratio 3.08;
p&lt;0.00001).</font><font style="font-size: 70%; vertical-align: top; color: #000000">4</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; background-color: #FFFFFF; font-family: Times New Roman; font-size: 13px">
Data will be presented at a forthcoming medical meeting and shared
with global regulatory authorities.</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="text-decoration: underline; color: #000000; font-weight: bold; font-family: Times New Roman; font-size: 13px">
Notes</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">
Gastric and gastroesophageal junction 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: 16px"><font style="color: #000000; font-size: 13px">
Gastric (stomach) cancer is the fifth most common cancer worldwide
and the fifth-highest leading cause of cancer
mortality.</font><font style="font-size: 70%; vertical-align: top; color: #000000">1</font><font style="color: #000000; font-family: Times New Roman">&#xA0;</font><font style="color: #000000; font-size: 13px">In
many regions, its incidence has been increasing in patients younger
than 50 years old, along with other gastrointestinal (GI)
malignancies.</font><font style="font-size: 70%; vertical-align: top; color: #000000">5</font><font style="color: #000000; font-family: Times New Roman">&#xA0;</font><font style="color: #000000; font-size: 13px">Nearly
one million new patients were diagnosed with gastric cancer in
2022, with approximately 660,000 deaths reported
globally.</font><font style="font-size: 70%; vertical-align: top; color: #000000">1</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">
GEJ cancer is a type of gastric cancer that arises from and spans
the area where the oesophagus connects to the
stomach.</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">
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<font style="font-family: Times New Roman; font-size: 16px"><font style="color: #000000; font-size: 13px">
Disease recurrence is common in patients with resectable gastric
cancer despite undergoing surgery with curative intent and
treatment with neoadjuvant/adjuvant
chemotherapy.</font><font style="color: #000000; font-family: Times New Roman">&#xA0;</font><font style="color: #000000; font-size: 13px">Approximately
one in four patients with gastric cancer who undergo surgery
develop recurrent disease within one year, and one in four patients
do not survive beyond two years, reflecting high unmet medical
need.</font><font style="font-size: 70%; vertical-align: top; color: #000000">7-8</font><font style="color: #000000; font-family: Times New Roman">&#xA0;</font><font style="color: #000000; font-size: 13px">Additionally,
the five-year survival rate remains poor, with less than half of
patients alive at five years.</font><font style="font-size: 70%; vertical-align: top; color: #000000">9</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; color: #000000; font-family: Times New Roman; font-size: 13px">
MATTERHORN</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">
MATTERHORN is a randomised, double-blind, placebo-controlled,
multi-centre, global Phase III trial
evaluating&#xA0;</font><font style="font-style: italic; color: #000000">Imfinzi</font><font style="color: #000000">&#xA0;as perioperative treatment for patients with
resectable Stage II-IVA gastric and GEJ cancers. Perioperative
therapy includes treatment before and after surgery, also known as
neoadjuvant/adjuvant therapy. In the trial, 948 patients were
randomised to receive a 1500mg fixed dose
of&#xA0;</font><font style="font-style: italic; color: #000000">Imfinzi</font><font style="color: #000000">&#xA0;plus FLOT chemotherapy or placebo plus FLOT
chemotherapy every four weeks for two cycles prior to surgery. This
was followed by&#xA0;</font><font style="font-style: italic; color: #000000">Imfinzi</font><font style="color: #000000">&#xA0;or placebo every four weeks for up to 12
cycles after surgery (including two cycles
of&#xA0;</font><font style="font-style: italic; color: #000000">Imfinzi</font><font style="color: #000000">&#xA0;or placebo plus FLOT chemotherapy and 10
additional cycles of&#xA0;</font><font style="font-style: italic; color: #000000">Imfinzi</font><font style="color: #000000">&#xA0;or placebo monotherapy).</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">
In the MATTERHORN trial, the primary endpoint is EFS, defined as
the time from randomisation until progression that precludes
surgery or requires non-protocol therapy, local or distant
recurrence or progression of disease, or death due to any cause as
assessed by blinded independent central review (BICR) according to
RECIST 1.1 and/or local pathology testing. Key secondary endpoints
include pCR rate, defined as the proportion of patients who have no
detectable cancer cells in resected tumour tissue following
neoadjuvant therapy, and OS. The trial enrolled participants in 176
centres in 20 countries, including in the US, Canada, Europe, South
America and Asia.</font></div>
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<font style="color: #000000; font-family: Times New Roman; font-size: 13px">
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<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; font-family: Times New Roman">&#xA0;</font><font style="color: #000000">(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="font-weight: bold; font-style: italic; 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; font-family: Times New Roman">&#xA0;</font><font style="color: #000000; background-color: #FFFFFF">is
approved in combination with chemotherapy (gemcitabine plus
cisplatin) in locally advanced or metastatic biliary tract cancer
(BTC) and in combination with&#xA0;</font><font style="font-style: italic; color: #000000; background-color: #FFFFFF">Imjudo</font><font style="color: #000000; font-family: Times New Roman">&#xA0;</font><font style="color: #000000">(tremelimumab)</font><font style="color: #000000; font-family: Times New Roman">&#xA0;</font><font style="color: #000000; background-color: #FFFFFF">in
unresectable hepatocellular carcinoma
(HCC).&#xA0;</font><font style="font-style: italic; color: #000000; background-color: #FFFFFF">Imfinzi</font><font style="color: #000000; background-color: #FFFFFF">&#xA0;is
also approved as a monotherapy in unresectable HCC in Japan and the
EU.</font></font></div>
<div style="text-align: justify; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="color: #242424; background-color: #FFFFFF; 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 addition to its indications in GI
cancers,&#xA0;</font><font style="font-style: italic; color: #000000">Imfinzi</font><font style="color: #000000">&#xA0;is the global standard of care based on OS
in the curative-intent setting of unresectable, Stage III non-small
cell lung cancer (NSCLC) in</font><font style="color: #000000; font-family: Times New Roman">&#xA0;</font><font style="color: #000000">patients
whose disease has not progressed after chemoradiotherapy
(CRT).</font><font style="color: #000000; font-family: Times New Roman">&#xA0;</font><font style="color: #000000">Additionally,&#xA0;</font><font style="font-style: italic; color: #000000">Imfinzi</font><font style="color: #000000">&#xA0;is
approved as a perioperative treatment in combination with
neoadjuvant chemotherapy in resectable non-small cell lung cancer
(NSCLC), and in combination with a short course
of&#xA0;</font><font style="font-style: italic; color: #000000">Imjudo</font><font style="color: #000000">&#xA0;and chemotherapy for the treatment of
metastatic NSCLC.</font><font style="color: #000000; font-family: Times New Roman">&#xA0;</font><font style="font-style: italic; color: #000000">Imfinzi</font><font style="color: #000000">&#xA0;is
also approved for limited-stage small cell lung cancer (SCLC) in
patients whose disease has not progressed following concurrent
platinum-based CRT; and</font><font style="color: #000000; font-family: Times New Roman">&#xA0;</font><font style="color: #000000">in
combination with chemotherapy (etoposide and either carboplatin or
cisplatin) for the treatment of extensive-stage
SCLC.</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; font-family: Times New Roman">&#xA0;</font><font style="color: #000000">in
combination with chemotherapy followed by&#xA0;</font><font style="font-style: italic; color: #000000">Imfinzi</font><font style="color: #000000">&#xA0;monotherapy is approved as a
1</font><font style="font-size: 70%; vertical-align: top; color: #000000">st</font><font style="color: #000000">-line
treatment for primary advanced or recurrent endometrial cancer
(mismatch repair deficient disease only in US and
EU).&#xA0;</font><font style="font-style: italic; color: #000000">Imfinzi</font><font style="color: #000000">&#xA0;in combination with chemotherapy followed
by&#xA0;</font><font style="font-style: italic; color: #000000">Lynparza&#xA0;</font><font style="color: #000000">(olaparib)
and&#xA0;</font><font style="font-style: italic; color: #000000">Imfinzi&#xA0;</font><font style="color: #000000">is
approved for patients with mismatch repair proficient advanced or
recurrent endometrial cancer in EU and Japan.</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">
Since the first approval in May 2017, more than 374,000 patients
have been treated with&#xA0;</font><font style="font-style: italic; color: #000000">Imfinzi</font><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
SCLC, NSCLC, bladder cancer, breast cancer, several GI and
gynaecologic cancers, 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">
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<font style="font-family: Times New Roman; font-size: 13px"><font style="font-weight: bold; color: #000000">
AstraZeneca in GI cancers</font><font style="color: #000000">&#xA0;</font></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
GI cancers across several medicines and a variety of tumour types
and stages of disease. In 2022, GI cancers collectively represented
approximately 5 million new cancer cases leading to approximately
3.3 million deaths.</font><font style="font-size: 70%; vertical-align: top; color: #000000">10</font></font></div>
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<font style="color: #000000; font-family: Times New Roman; font-size: 13px">
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<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 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 addition to its indications in BTC and
HCC,&#xA0;</font><font style="font-style: italic; color: #000000">Imfinzi</font><font style="color: #000000">&#xA0;is being assessed in combinations, including
with&#xA0;</font><font style="font-style: italic; color: #000000">Imjudo</font><font style="color: #000000">, in liver, 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="color: #000000; font-family: Times New Roman; font-size: 13px">
The Company is also assessing rilvegostomig (AZD2936), a PD-1/TIGIT
bispecific antibody, in combination with chemotherapy as an
adjuvant therapy in BTC and as a 1st-line treatment in patients
with HER2-negative, locally advanced unresectable or metastatic
gastric and GEJ cancers.</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: 16px"><font style="font-style: italic; color: #000000; font-size: 13px">
Enhertu</font><font style="color: #000000; font-family: Times New Roman">&#xA0;</font><font style="color: #000000; font-size: 13px">(trastuzumab
deruxtecan), a HER2-directed antibody drug conjugate, is approved
in the US and several other countries for HER2-positive advanced
gastric cancer.&#xA0;</font><font style="font-style: italic; color: #000000; font-size: 13px">Enhertu</font><font style="color: #000000; font-size: 13px">&#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</font><font style="color: #000000">, a first-in-class PARP
inhibitor, is approved the US and several other countries for the
treatment of BRCA-mutated metastatic pancreatic
cancer.&#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="color: #000000; font-family: Times New Roman; font-size: 13px">
AstraZeneca is advancing multiple modalities that provide
complementary mechanisms for targeting Claudin 18.2, a promising
therapeutic target in gastric cancer. These include AZD0901, a
potential first-in-class antibody drug conjugate licensed from KYM
Biosciences Inc., currently in Phase III development; AZD5863, a
novel Claudin 18.2/CD3 T-cell engager bispecific antibody licensed
from Harbour Biomed in Phase I development; and AZD6422, an
armoured autologous chimeric antigen receptor T-cell (CAR T)
therapy, currently being evaluated in an Investigator Initiated
Trial (IIT) in collaboration with AbelZeta in China.</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 early development, AstraZeneca is developing two Glypican 3
(GPC3) armoured CAR Ts in HCC. AZD5851, currently in Phase I
development, is being developed globally, and C-CAR031 / AZD7003 is
being co-developed with AbelZeta in China where it is under
evaluation in an IIT.</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 immuno-oncology (IO)</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 a pioneer in introducing the concept of
immunotherapy into dedicated clinical areas of high unmet medical
need. The Company has a comprehensive and diverse IO portfolio and
pipeline anchored in immunotherapies designed to overcome evasion
of the anti-tumour immune response and stimulate the body's immune
system to attack 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-family: Times New Roman; font-size: 13px"><font style="color: #000000">
AstraZeneca strives to redefine cancer care and help transform
outcomes for patients with&#xA0;</font><font style="font-style: italic; color: #000000">Imfinzi</font><font style="color: #000000">&#xA0;as a monotherapy and in combination
with&#xA0;</font><font style="font-style: italic; color: #000000">Imjudo</font><font style="color: #000000">&#xA0;as well as other novel immunotherapies and
modalities. The Company is also investigating next-generation
immunotherapies like bispecific antibodies and therapeutics that
harness different aspects of immunity to target cancer, including
cell therapy and T-cell engagers.</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">
AstraZeneca is pursuing an innovative clinical strategy to bring
IO-based therapies that deliver long-term survival to new settings
across a wide range of cancer types. The Company is focused on
exploring novel combination approaches to help prevent treatment
resistance and drive longer immune responses. With an extensive
clinical programme, the Company also champions the use of IO
treatment in earlier disease stages, where there is the greatest
potential for cure.&#x202F;</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>
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<font style="font-family: Times New Roman; font-size: 13px"><font style="font-weight: bold; color: #000000">
AstraZeneca</font><font style="color: #000000">&#x202F;</font></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's innovative
medicines are sold in more than 125 countries and 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 social media</font><font style="color: #68D2DF">&#xA0;</font><font style="text-decoration: underline; color: #0000FF">@AstraZeneca</font><font style="color: #000000">.&#xA0;</font></font></div>
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Contacts</font></div>
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For details on how to contact the Investor Relations Team, please
click</font><font style="color: #000000; font-family: Times New Roman">&#xA0;</font><font style="text-decoration: underline; color: #0000FF; background-color: #FFFFFF">here</font><font style="color: #000000">.
For Media contacts, click</font><font style="color: #000000; font-family: Times New Roman">&#xA0;</font><font style="text-decoration: underline; color: #0000FF; background-color: #FFFFFF">here</font><font style="color: #000000">.</font></font></div>
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References</font></div>
<div style="text-align: left; margin-left: 24px; margin-right: 0px; text-indent: -24px">
<font style="font-family: Times New Roman; font-size: 16px"><font style="color: #000000; font-size: 13px">1.&#xA0;&#xA0;</font><font style="color: #000000; font-family: Times New Roman">&#xA0;</font><font style="color: #000000; font-size: 13px">World
Health Organization. International Agency for Research on Cancer.
Stomach Fact Sheet. Available at:</font><font style="color: #000000; font-family: Times New Roman">&#xA0;</font><font style="text-decoration: underline; color: #0000FF; font-size: 13px">https://gco.iarc.who.int/media/globocan/factsheets/cancers/7-stomach-fact-sheet.pdf</font><font style="color: #000000; font-size: 13px">.
Accessed March 2025.</font></font></div>
<div style="text-align: left; margin-left: 24px; margin-right: 0px; text-indent: -24px">
<font style="font-family: Times New Roman; font-size: 13px"><font style="color: #000000; font-size: 13px">2.&#xA0;&#xA0;</font><font style="color: #000000; font-family: Times New Roman">&#xA0;</font><font style="color: #000000; font-size: 13px">AstraZeneca
PLC. Investor Relations Epidemiology Spreadsheet. Available
at:</font><font style="color: #000000; font-family: Times New Roman">&#xA0;</font><font style="text-decoration: underline; color: #0000FF; font-size: 13px">https://www.astrazeneca.com/investor-relations.html</font><font style="color: #000000; font-size: 13px">.
Accessed March 2025.</font></font></div>
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Health, validated with SEER stage at diagnosis and Cabasag et al.
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YY, et al. LBA73 Pathological complete response (pCR) to durvalumab
plus 5-fluorouracil, leucovorin, oxaliplatin and docetaxel (FLOT)
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Cancer Institute. Gastroesophageal junction. Available
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Y,&#xA0;et al. Postoperative recurrence of gastric cancer depends
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<font style="font-family: Times New Roman; font-size: 16px"><font style="color: #000000; font-size: 13px">8.&#xA0;&#xA0;</font><font style="color: #000000; font-family: Times New Roman">&#xA0;</font><font style="color: #000000; font-size: 13px">Ilic
M, Ilic I. Epidemiology of stomach cancer.&#xA0;</font><font style="font-style: italic; color: #000000; font-size: 13px">World J
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<font style="font-family: Times New Roman; font-size: 16px"><font style="color: #000000; font-size: 13px">9.&#xA0;&#xA0;</font><font style="color: #000000; font-family: Times New Roman">&#xA0;</font><font style="color: #000000; font-size: 13px">Al-Batran
SE, et al. Perioperative chemotherapy with fluorouracil plus
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<div style="text-align: left; margin-left: 24px; margin-right: 0px; text-indent: -24px">
<font style="font-family: Times New Roman; font-size: 16px"><font style="color: #000000; font-size: 13px">10.&#xA0;</font><font style="color: #000000; font-family: Times New Roman">&#xA0;</font><font style="color: #000000; font-size: 13px">World
Health Organization. World Cancer Fact Sheet. Available
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<div style="text-align: left; margin-left: 24px; margin-right: 0px; text-indent: 0px">
<font style="color: #000000; font-family: Times New Roman; font-size: 13px">Accessed
March 2025.</font></div>
<div style="text-align: left; margin-left: 24px; 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: left; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="color: #000000; font-family: Times New Roman; font-size: 13px">
Dr. Janjigian provides consulting and advisory services to
AstraZeneca.</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">
&#xA0;</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">
Adrian Kemp</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">
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="font-family: Times New Roman; font-size: 13px">&#xA0;</font></div>
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<font style="font-style: italic; color: #000000; font-family: Times New Roman; font-size: 13px">
&#xA0;</font></div>
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<font style="text-decoration: underline; font-family: Times New Roman; font-size: 13px">
SIGNATURES</font></div>
<div><font style="font-family: Times New Roman; font-size: 10">&#xA0;</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>
<div><font style="font-family: Times New Roman; font-size: 10">&#xA0;</font></div>
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<div style="text-align: left; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-family: Times New Roman; font-size: 13px">AstraZeneca
PLC</font></div>
</td>
</tr></table>
</div>
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<font style="font-family: Times New Roman; font-size: 13px">&#xA0;</font></div>
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<div style="text-align: left; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-family: Times New Roman; font-size: 13px">Date:
<font style="font-size: 13px">07 March 2025</font></font></div>
<div><font style="font-family: Times New Roman; font-size: 10">&#xA0;</font></div>
<div>
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<div><font style="font-family: Times New Roman; font-size: 13px">&#xA0;</font></div>
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<div style="text-align: left; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-family: Times New Roman; font-size: 13px">By: /s/
Adrian Kemp</font></div>
</td>
</tr><tr>
<td style="vertical-align: top; width: 71%">
<div><font style="font-family: Times New Roman; font-size: 13px">&#xA0;</font></div>
</td>
<td style="vertical-align: top; width: 29%">
<div style="text-align: left; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-family: Times New Roman; font-size: 13px">Name:
Adrian Kemp</font></div>
</td>
</tr><tr>
<td style="vertical-align: top; width: 71%">
<div><font style="font-family: Times New Roman; font-size: 13px">&#xA0;</font></div>
</td>
<td style="vertical-align: top; width: 29%">
<div style="text-align: left; margin-left: 0px; margin-right: 0px; text-indent: 0px">
<font style="font-family: Times New Roman; font-size: 13px">Title:
Company Secretary</font></div>
</td>
</tr></table>
</div>
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