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.
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References
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Available at: https://www.astrazeneca.com/investor-relations.html.
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Cabasag et al. and Kuzuu et al. 2021.
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Accessed March 2025.
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Accessed March 2025.
Dr. Janjigian provides consulting and
advisory services to AstraZeneca.
Adrian Kemp
Company Secretary
AstraZeneca PLC
