REG - AstraZeneca PLC - Imfinzi improved EFS in early-stage gastric cancer

AstraZenecaAnnouncement

07/03/2025 07:15

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RNS Number : 8003Z  AstraZeneca PLC  07 March 2025

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
(https://www.astrazeneca.com/media-centre/press-releases/2023/imfinzi-plus-chemotherapy-doubled-pathologic-complete-response-rate-resectable-early-stage-gastric-gastroesophageal-junction-cancers-vs-chemotherapy.html)
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 1(st)-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 (http://www.astrazeneca.com/)  and follow the
Company on social media @AstraZeneca
(https://www.linkedin.com/company/astrazeneca) .

 

Contacts

For details on how to contact the Investor Relations Team, please click here
(https://www.astrazeneca.com/investor-relations.html#Contacts) . For Media
contacts, click here (https://www.astrazeneca.com/media-centre/contacts.html)
.

 

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
(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
(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
(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
(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

 

 

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