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 March 2025
Commission
File Number: 001-11960
AstraZeneca PLC
1
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Cambridge
Biomedical Campus
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United
Kingdom
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AstraZeneca PLC
INDEX
TO EXHIBITS
1.
Imfinzi improved EFS in early-stage gastric cancer
7 March 2025
Imfinzi-based regimen
demonstrated statistically significant and clinically meaningful
improvement in event-free survival in resectable early-stage
gastric and gastroesophageal junction cancers
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
Imfinzi plus chemotherapy more than doubled pathologic
complete response rate in previously reported analysis of this
trial in 2023
Positive high-level results from the MATTERHORN Phase III trial
showed perioperative treatment with
AstraZeneca's Imfinzi (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 Imfinzi in combination with
chemotherapy before
surgery, followed by adjuvant Imfinzi in combination with chemotherapy,
then Imfinzi 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.
For the secondary endpoint of overall survival (OS), a strong trend
was observed in favour of the Imfinzi-based regimen at this interim analysis. The trial
will continue to follow OS, which will be formally assessed at the
final analysis.
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 43,000 drug-treated patients in the US,
European Union (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 2030.3
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: "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 clinically
meaningful improvement in patient outcomes, including decreasing
the risk of the cancer coming back."
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. This
perioperative approach with Imfinzi underscores our commitment to moving into
earlier stages of cancer where novel therapies can have the biggest
impact on patients' lives."
The safety profile for Imfinzi and FLOT chemotherapy was consistent with
the known profiles of each medicine, and there were no new safety
findings.
In a previously
reported interim
analysis for the key secondary endpoint of pathologic complete
response (pCR), the Imfinzi combination more
than doubled the pCR rate compared to neoadjuvant chemotherapy
alone (19% versus 7%, odds ratio 3.08;
p<0.00001).4
Data will be presented at a forthcoming medical meeting and shared
with global regulatory authorities.
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 In
many regions, its incidence has been increasing in patients younger
than 50 years old, along with other gastrointestinal (GI)
malignancies.5 Nearly
one million new patients were diagnosed with gastric cancer in
2022, with approximately 660,000 deaths reported
globally.1
GEJ cancer is a type of gastric cancer that arises from and spans
the area where the oesophagus connects to the
stomach.6
Disease recurrence is common in patients with resectable gastric
cancer despite undergoing surgery with curative intent and
treatment with neoadjuvant/adjuvant
chemotherapy. 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.7-8 Additionally,
the five-year survival rate remains poor, with less than half of
patients alive at five years.9
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
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.
Imfinzi
Imfinzi (durvalumab)
is a human monoclonal antibody that binds to the PD-L1 protein and
blocks the interaction of PD-L1 with the PD-1 and CD80 proteins,
countering the tumour's immune-evading tactics and releasing the
inhibition of immune responses.
Imfinzi is
approved in combination with chemotherapy (gemcitabine plus
cisplatin) 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 non-small cell lung cancer
(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 (etoposide and either carboplatin or
cisplatin) for the treatment of extensive-stage
SCLC.
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 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 EU and Japan.
Since the first approval in May 2017, more than 374,000 patients
have been treated with Imfinzi. As part of a broad development
programme, Imfinzi is being tested as a single treatment and in
combinations with other anti-cancer treatments for patients with
SCLC, NSCLC, bladder cancer, breast cancer, several GI and
gynaecologic cancers, and other solid tumours.
AstraZeneca in GI cancers
AstraZeneca has a broad development programme for the treatment of
GI cancers across several medicines and a variety of tumour types
and stages of disease. In 2022, GI cancers collectively represented
approximately 5 million new cancer cases leading to approximately
3.3 million deaths.10
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.
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.
Enhertu (trastuzumab
deruxtecan), a HER2-directed antibody drug conjugate, 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 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).
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.
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.
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 March 2025.
2. AstraZeneca
PLC. Investor Relations Epidemiology Spreadsheet. Available
at: https://www.astrazeneca.com/investor-relations.html.
Accessed March 2025.
3. Kantar
Health, validated with SEER stage at diagnosis and Cabasag et al.
and Kuzuu et al. 2021.
4. Janjigian
YY, et al. LBA73 Pathological complete response (pCR) to durvalumab
plus 5-fluorouracil, leucovorin, oxaliplatin and docetaxel (FLOT)
in resectable gastric and gastroesophageal junction cancer
(GC/GEJC): Interim results of the global, phase III MATTERHORN
study. Ann
Oncol.
2023;34(S2):S1315 - S1316.
5. 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.
6. National
Cancer Institute. Gastroesophageal junction. Available
at: https://www.cancer.gov/publications/dictionaries/cancer-terms/def/gastroesophageal-junction.
Accessed March 2025.
7. 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.
8. Ilic
M, Ilic I. Epidemiology of stomach cancer. World J
Gastroenterol.
2022;28(12):1187-1203.
9. Al-Batran
SE, et al. Perioperative chemotherapy with fluorouracil plus
leucovorin, oxaliplatin, and docetaxel versus fluorouracil or
capecitabine plus cisplatin and epirubicin for locally advanced,
resectable gastric or gastro-oesophageal junction adenocarcinoma
(FLOT4): a randomised, phase 2/3 trial. Lancet. 2019;393(10184):1948-1957.
10. World
Health Organization. World Cancer Fact Sheet. Available
at https://gco.iarc.who.int/media/globocan/factsheets/populations/900-world-fact-sheet.pdf
Accessed
March 2025.
Dr. Janjigian provides consulting and advisory services to
AstraZeneca.
Adrian Kemp
Company Secretary
AstraZeneca PLC
SIGNATURES
Pursuant
to the requirements of the Securities Exchange Act of 1934, the
Registrant has duly caused this report to be signed on its behalf
by the undersigned, thereunto duly authorized.
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AstraZeneca
PLC
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Date:
07 March 2025
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By: /s/
Adrian Kemp
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Name:
Adrian Kemp
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Title:
Company Secretary
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