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 November 2025
Commission
File Number: 001-11960
AstraZeneca PLC
1
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AstraZeneca PLC
INDEX
TO EXHIBITS
1.
Imfinzi approved in US for early gastric cancer
26 November
2025
Imfinzi approved
in the US as first and only perioperative immunotherapy for
patients with early
gastric and gastroesophageal cancers
Based on MATTERHORN Phase III trial results which showed a
29% reduction in the risk of progression, recurrence or death and a
22% reduction in the risk of death for the Imfinzi regimen vs.
chemotherapy alone
AstraZeneca's Imfinzi (durvalumab) in
combination with standard-of-care FLOT chemotherapy (fluorouracil,
leucovorin, oxaliplatin, and docetaxel) has
been approved in the US for the treatment of adult
patients with
resectable, early-stage and locally advanced (Stages II, III, IVA)
gastric and gastroesophageal junction (GEJ) cancers. The approved
regimen includes neoadjuvant Imfinzi in
combination with chemotherapy before surgery, followed by
adjuvant Imfinzi in
combination with chemotherapy, then Imfinzi monotherapy.
The approval follows Priority
Review by
the Food and Drug Administration (FDA) and is based on event-free
survival (EFS) and overall survival (OS) data from the MATTERHORN
Phase III trial. The
EFS results were presented during the Plenary Session at the
2025 American Society of Clinical Oncology (ASCO) Annual Meeting
and simultaneously published in The
New England Journal of Medicine. OS
results from MATTERHORN were presented in a Proffered Paper
session at the European Society for Medical Oncology (ESMO)
Congress 2025.
Gastric cancer is the fifth leading cause of cancer death globally,
with nearly one million people diagnosed each
year.1 In
2024, there were roughly 6,500 drug-treated patients in the US in
early-stage and locally advanced gastric or GEJ
cancer.2
Dave Fredrickson, Executive Vice President,
Oncology Haematology Business
Unit, AstraZeneca, said: "This approval ushers in a new
clinical paradigm for patients with early gastric and
gastroesophageal junction cancers, with Imfinzi plus
FLOT delivering a durable survival benefit that increases over
time. As the third US approval for a
perioperative Imfinzi-based
regimen, this milestone further validates the perioperative
approach and underscores our focus on bringing novel treatments to
early-stage cancers where cure is the goal."
Yelena Y. Janjigian, MD, Chief Attending Physician of the
Gastrointestinal Medical Oncology Service, Memorial Sloan Kettering
Cancer Center (MSK), New York and principal investigator in the
MATTERHORN trial, said: "Today's approval marks the first
immunotherapy regimen approved in the neoadjuvant setting for
gastric and gastroesophageal junction cancers-with durvalumab
demonstrating a clear overall survival benefit and opening an
entirely new chapter in the treatment of early-stage
disease. Nearly
seven in 10 patients were alive at three years following treatment
with the durvalumab-based perioperative regimen. This survival
benefit, observed regardless of PD-L1 status, establishes a new
standard of care in this curative-intent
setting."
Aki Smith, Founder and Executive Director, Hope for Stomach Cancer,
said: "From personal experience as a caregiver to my father, I know
that for too long patients diagnosed with early gastric or
gastroesophageal junction cancer have faced a high risk of their
cancer returning, even after undergoing surgery and therapy
intended to cure it. Today's approval represents a major step
forward in improving outcomes and offering renewed hope to those
affected by this devastating disease."
In a planned interim analysis, patients treated with
the Imfinzi-based perioperative regimen showed a 29%
reduction in the risk of disease progression, recurrence or death
versus chemotherapy alone (based on an EFS hazard ratio [HR] of
0.71; 95% confidence interval [CI] 0.58-0.86; p<0.001).
Estimated median EFS was not yet reached for
the Imfinzi arm versus 32.8 months for the comparator
arm. An estimated 78.2% of patients treated with
the Imfinzi-based perioperative regimen were event-free at
one year, compared to 74.0% in the comparator arm; the estimated
24-month EFS rate was 67.4% versus 58.5%,
respectively.
In the final OS analysis, results showed
the Imfinzi and FLOT perioperative regimen reduced the
risk of death by 22% compared with chemotherapy alone (based on a
HR of 0.78; 95% CI 0.63-0.96; p=0.021). An estimated 69% of
patients treated with the Imfinzi-based regimen were alive at three years compared
with 62% in the FLOT-only arm. With longer follow-up, the OS curves
showed continued separation, signaling a greater magnitude of
benefit over time for the Imfinzi-based regimen. An OS benefit was observed
regardless of PD-L1 status.
The safety profile for Imfinzi and FLOT chemotherapy was consistent with
the known profiles of each medicine, and the percentage of patients
that completed surgery was similar compared to chemotherapy alone.
Grade 3 or higher adverse events due to any cause were similar
between the two arms (71.6% for Imfinzi and FLOT arm; 71.2% for FLOT-only
arm).
The US regulatory submission was reviewed under Project Orbis,
which provides a framework for concurrent submission and review of
oncology medicines among participating international partners. As
part of Project Orbis, the Imfinzi and FLOT perioperative regimen is also under
review by regulatory authorities in Australia, Canada, and
Switzerland for the same indication. Regulatory applications are
also under review in the European Union (EU), Japan and several
other countries.
Notes
Gastric and gastroesophageal junction cancers
Gastric (stomach) cancer is the fifth most common cancer worldwide
and the fifth-highest leading cause of cancer
mortality.1 Nearly
one million new patients were diagnosed with gastric cancer in
2022, with approximately 660,000 deaths reported
globally.1 In
many regions, its incidence has been increasing in patients younger
than 50 years old, along with other gastrointestinal (GI)
malignancies.3 In
2024, there were roughly 43,000 drug-treated patients in the US, EU
and Japan in early-stage and locally advanced gastric or GEJ
cancer.2 Approximately
62,000 patients in these regions are expected to be newly diagnosed
in this setting by 2030.4
GEJ cancer is a type of gastric cancer that arises from and spans
the area where the oesophagus connects to the
stomach.5
Disease recurrence is common in patients with resectable gastric
cancer despite undergoing surgery with curative intent and
treatment with neoadjuvant/adjuvant
chemotherapy.6 Approximately
one in four patients with gastric cancer who undergo surgery
develop recurrent disease within one year, and the five-year
survival rate remains poor, with less than half of patients alive
at five years.6-7
MATTERHORN
MATTERHORN is a randomised, double-blind, placebo-controlled,
multi-centre, global Phase III trial
evaluating Imfinzi 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 Imfinzi plus FLOT chemotherapy or placebo plus FLOT
chemotherapy every four weeks for two cycles prior to surgery. This
was followed by Imfinzi or placebo every four weeks for up to 12
cycles after surgery (including two cycles
of Imfinzi or placebo plus FLOT chemotherapy and 10
additional cycles of Imfinzi or placebo monotherapy).
In the MATTERHORN trial, the primary endpoint is EFS, defined as
time from randomisation until the date of one of the following
events (whichever occurred first): RECIST (version 1.1, per blinded
independent central review assessment) progression that precludes
surgery or requires non-protocol therapy during the neoadjuvant
period; RECIST progression/recurrence during the adjuvant period;
non-RECIST progression that precludes surgery or requires
non-protocol therapy during the neoadjuvant period or discovered
during surgery; progression/recurrence confirmed by biopsy
post-surgery; or death due to any cause. Key secondary endpoints
include pathologic complete response 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.
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.
In GI cancer, Imfinzi is approved in combination with chemotherapy
in locally advanced or metastatic biliary tract cancer (BTC) and in
combination with Imjudo (tremelimumab) in unresectable
hepatocellular carcinoma (HCC). Imfinzi is also approved as a monotherapy in
unresectable HCC in Japan and the EU.
In addition to its indications in GI
cancers, Imfinzi 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 patients whose disease has not
progressed after chemoradiotherapy (CRT).
Additionally, Imfinzi is approved as a perioperative treatment in
combination with neoadjuvant chemotherapy in resectable NSCLC, and
in combination with a short course of Imjudo and chemotherapy for the treatment of
metastatic NSCLC. Imfinzi is also approved for limited-stage small
cell lung cancer (SCLC) in patients whose disease has not
progressed following concurrent platinum-based CRT; and in
combination with chemotherapy for the treatment of extensive-stage
SCLC.
Perioperative Imfinzi in combination with neoadjuvant chemotherapy
is approved in the US, EU, Japan and other countries for patients
with muscle-invasive bladder cancer based on results from the
NIAGARA Phase III trial. Additionally, in May
2025, Imfinzi added to Bacillus Calmette-Guérin
induction and maintenance therapy met the primary endpoint of
disease-free survival for patients with high-risk
non-muscle-invasive bladder cancer in the POTOMAC Phase III
trial.
Imfinzi in
combination with chemotherapy followed by Imfinzi monotherapy is approved as a 1st-line
treatment for primary advanced or recurrent endometrial cancer
(mismatch repair deficient disease only in the US and
EU). Imfinzi in combination with chemotherapy followed
by Lynparza (olaparib) and Imfinzi is approved for patients with mismatch
repair proficient advanced or recurrent endometrial cancer in the
EU and Japan.
Since the first approval in May 2017, more than 414,000 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
NSCLC, bladder cancer, breast cancer, ovarian cancer and several GI
cancers.
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 2022, GI cancers collectively represented
approximately 5 million new cancer cases leading to approximately
3.3 million deaths.8
Within this programme, the Company is committed to improving
outcomes in gastric, liver, biliary tract, oesophageal, pancreatic,
and colorectal cancers.
In addition to its indications in BTC and
HCC, Imfinzi is being assessed in combinations, including
with Imjudo, in liver, oesophageal and gastric cancers in an
extensive development programme spanning early to late-stage
disease across settings.
Enhertu (trastuzumab
deruxtecan), a HER2-directed antibody drug conjugate (ADC), is
approved in the US and several other countries for HER2-positive
advanced gastric cancer. Enhertu is jointly developed and commercialised by
AstraZeneca and Daiichi Sankyo.
Lynparza, a first-in-class PARP
inhibitor, is approved in the US and several other countries for
the treatment of BRCA-mutated metastatic pancreatic
cancer. Lynparza is developed and commercialised in
collaboration with MSD (Merck & Co., Inc. inside the US and
Canada).
The Company is also assessing rilvegostomig (AZD2936), a PD-1/TIGIT
bispecific antibody, in combination with chemotherapy as an
adjuvant therapy in BTC, in combination with bevacizumab with or
without Imjudo as a 1st-line treatment in patients with
advanced HCC, and as a 1st-line treatment in patients with
HER2-negative, locally advanced unresectable or metastatic gastric
and GEJ cancers. Rilvegostomig is also being evaluated in
combination with Enhertu in previously untreated, HER2-expressing,
locally advanced or metastatic BTC.
AstraZeneca is advancing multiple modalities that provide
complementary mechanisms for targeting Claudin 18.2, a promising
therapeutic target in gastric cancer. These include sonesitatug
vedotin, a potential first-in-class ADC 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 AZD4360, an
antibody drug conjugate, currently being evaluated in a Phase I/II
trial in patients with advanced solid tumours.
In early development, AstraZeneca is developing C-CAR031 / AZD7003,
a Glypican 3 (GPC3) armoured CAR T, in HCC. C-CAR031 / AZD7003is
being co-developed with AbelZeta in China where it is under
evaluation in an IIT.
AstraZeneca in immuno-oncology (IO)
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.
AstraZeneca strives to redefine cancer care and help transform
outcomes for patients with Imfinzi as a monotherapy and in combination
with Imjudo 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.
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.
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's innovative
medicines are sold in more than 125 countries and used by millions
of patients worldwide. Please visit astrazeneca.com and
follow the Company on Social Media @AstraZeneca.
Contacts
For details on how to contact the Investor Relations Team, please
click here.
For Media contacts, click here.
References
1. World Health
Organization. International Agency for Research on Cancer. Stomach
Fact Sheet. Available at: https://gco.iarc.who.int/media/globocan/factsheets/cancers/7-stomach-fact-sheet.pdf.
Accessed November 2025.
2. AstraZeneca PLC.
Investor Relations Epidemiology Spreadsheet. Available
at: https://www.astrazeneca.com/investor-relations.html.
Accessed November 2025.
3. Li Y, et al. Global burden of
young-onset gastric cancer: a systematic trend analysis of the
global burden of disease study 2019. Gastric
Cancer.
2024;27(4):684-700.
4.
Kantar Health, validated with SEER stage at diagnosis and Cabasag
et al. And Kuzuu et al. 2021.
5. National Cancer
Institute. Gastroesophageal junction. Available
at: https://www.cancer.gov/publications/dictionaries/cancer-terms/def/gastroesophageal-junction.
Accessed November 2025.
6. Li Y, et al. Postoperative
recurrence of gastric cancer depends on whether the chemotherapy
cycle was more than 9 cycles. Medicine. 2022;101(5):e28620.
7. Ilic M, Ilic I. Epidemiology of
stomach cancer. World J
Gastroenterol.
2022;28(12):1187-1203.
8. World Health
Organization. World Cancer Fact Sheet. Available
at: https://gco.iarc.who.int/media/globocan/factsheets/populations/900-world-fact-sheet.pdf.
Accessed November 2025.
MSK Disclosure: Dr. Janjigian provides consulting and advisory
services to AstraZeneca.
Matthew Bowden
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.
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AstraZeneca
PLC
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Date: 26 November 2025
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By: /s/
Matthew Bowden
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Name:
Matthew Bowden
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Title:
Company Secretary
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