REG - AstraZeneca PLC - Imfinzi improved pCR in gastric and GEJ cancers

AstraZenecaAnnouncement

02/06/2023 17:00

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RNS Number : 5524B  AstraZeneca PLC  02 June 2023

 

2 June 2023

 

Imfinzi plus chemotherapy significantly improved pathologic complete response
in gastric and gastroesophageal junction cancers in MATTERHORN Phase III trial

 

First global Phase III trial of immunotherapy and chemotherapy

combination to demonstrate clinical benefit in this setting

 

Trial will continue to assess event-free survival

 

Positive high-level results from a planned interim analysis of the MATTERHORN
Phase III trial showed treatment with AstraZeneca's Imfinzi (durvalumab)
added to standard-of-care FLOT (fluorouracil, leucovorin, oxaliplatin, and
docetaxel) neoadjuvant (before surgery) chemotherapy demonstrated a
statistically significant and clinically meaningful improvement in the key
secondary endpoint of pathologic complete response (pCR) versus neoadjuvant
chemotherapy alone for patients with resectable, early-stage and locally
advanced (Stages II, III, IVA) gastric and gastroesophageal junction (GEJ)
cancers.

The trial will continue as planned to assess EFS and overall survival to which
the trial team, investigators and participants remain blinded.

The safety and tolerability of adding Imfinzi to neoadjuvant FLOT chemotherapy
was consistent with the known profile of this combination and did not decrease
the number of patients able to undergo surgery versus chemotherapy alone.

 

Josep Tabernero, MD, PhD, head of the Medical Oncology Department, Vall
d'Hebron University Hospital, Barcelona, Spain, and principal investigator of
the MATTERHORN trial, said: "Patients with resectable gastric and
gastroesophageal junction cancers urgently need better treatment options,
because today, one in four patients still progress within one year even after
surgery with curative intent. These results demonstrate an increase in
pathologic complete response after adding durvalumab treatment to FLOT
chemotherapy and surgery. This is an encouraging early sign that this regimen
may deliver long-term clinical benefit for these patients, as pathologic
complete response has been correlated with both event-free and overall
survival in multiple settings."

 

Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca,
said: "These early results from MATTERHORN support harnessing the immune
system together with chemotherapy and surgery as a new treatment approach to
improve outcomes for patients with earlier stages of gastric and
gastroesophageal junction cancers. These findings reinforce our focus on
delivering novel Imfinzi-based treatments that have the potential to redefine
care for patients with gastrointestinal cancers."

 

Gastric cancer is the fourth leading cause of cancer death globally, with more
than one million people diagnosed each year. By 2030, approximately 70,000
patients in the US, EU and Japan will be newly diagnosed with Stage II-III
gastric or GEJ cancers.(1) Approximately one in four patients with gastric
cancer who undergo surgery with curative intent develop recurrent disease
within one year, reflecting a high unmet medical need.(2)

These data will be shared with health authorities and presented at a
forthcoming medical meeting.

Notes

Gastric and gastroesophageal junction cancers

Gastric (stomach) cancer is the fifth most common cancer worldwide and the
fourth highest leading cause of cancer mortality.(3) Approximately one million
new patients were diagnosed with gastric cancer in 2020, with 768,000 deaths
reported globally.(3)

GEJ cancer is a type of gastric cancer that arises from and spans the area
where the esophagus connects to the stomach.(4)

Disease recurrence is common in patients with resectable gastric cancer
despite undergoing curative-intent surgery and treatment with
neoadjuvant/adjuvant chemotherapy.(2) Additionally, the five-year survival
rate for gastric cancer remains poor, with only up to a third of patients
alive at five years.(5,6)

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 gastroesophageal cancers.
Perioperative therapy includes treatment before and after surgery, also known
as neoadjuvant/adjuvant therapy. In the trial, 958 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, 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 disease progression or death. 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
overall survival (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) in the US, EU, Japan and several other countries based on the
TOPAZ-1 and HIMALAYA Phase III trials, respectively.

 

In addition to its indications in gastrointestinal (GI) cancers, Imfinzi is
the only approved immunotherapy and the global standard of care in the
curative-intent setting of unresectable, Stage III non-small cell lung cancer
(NSCLC) in patients whose disease has not progressed after chemoradiation
therapy based on the PACIFIC Phase III trial.

 

Imfinzi is also approved in the US, EU, Japan, China and many other countries
around the world for the treatment of extensive-stage small-cell lung cancer
(SCLC) based on the CASPIAN Phase III trial. Additionally, Imfinzi is approved
in combination with a short course of Imjudo and chemotherapy for the
treatment of metastatic NSCLC in the US, EU and Japan based on the POSEIDON
Phase III trial. Imfinzi is approved in previously treated patients with
advanced bladder cancer in a small number of countries.

 

Since the first approval in May 2017, more than 200,000 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, several GI cancers, ovarian cancer,
endometrial cancer and other solid tumours.

 

In GI cancers specifically, AstraZeneca has several ongoing registrational
trials investigating Imfinzi across multiple liver cancer settings (EMERALD-1,
EMERALD-2 and EMERALD-3) and in locally advanced esophageal cancer (KUNLUN).

 

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 2020, GI cancers collectively represented approximately 5.1 million new
cancer cases leading to approximately 3.6 million deaths.(7)

 

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, is
approved in the US and several other countries for HER2-positive advanced
gastric cancer and is being assessed in colorectal cancer. Enhertu is jointly
developed and commercialised by AstraZeneca and Daiichi Sankyo.

 

Lynparza (olaparib), 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 also recently entered into a global exclusive license agreement
with KYM Biosciences Inc. for CMG901. CMG901 is a potential first-in-class
antibody drug conjugate targeting Claudin 18.2, a promising therapeutic target
in gastric cancer, currently in Phase I development.

 

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 aims to reimagine cancer care and help transform outcomes for
patients with Imfinzi as a single treatment and in combination with Imjudo as
well as other novel immunotherapies and modalities. The Company is also
exploring next-generation immunotherapies like bispecific antibodies and
therapeutics that harness different aspects of immunity to target cancer.

 

AstraZeneca is boldly 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. 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 operates in over 100 countries
and its innovative medicines are used by millions of patients worldwide.
Please visit astrazeneca.com
(https://www.astrazeneca.com/media-centre/press-releases/2021/imfinzi-improved-survival-in-biliary-tract-cancer.html)
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Contacts

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References

1.   Kantar Health, validated with SEER stage at diagnosis and Cabasag et
al. and Kuzuu et al. 2021

2.   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.

3.   World Health Organisation. International Agency for Research on Cancer.
Stomach Fact Sheet. Available at:
https://gco.iarc.fr/today/data/factsheets/cancers/7-Stomach-fact-sheet.pdf
(https://gco.iarc.fr/today/data/factsheets/cancers/7-Stomach-fact-sheet.pdf) .
Accessed May 2023.

4.   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)
.

5.   American Cancer Society. Stomach Cancer Survival Rates. Available at:
https://www.cancer.org/cancer/types/stomach-cancer/detection-diagnosis-staging/survival-rates.html
(https://www.cancer.org/cancer/types/stomach-cancer/detection-diagnosis-staging/survival-rates.html)
. Accessed May 2023.

6.   Cancer Research UK. Survival for stomach cancer. Available at:
https://www.cancerresearchuk.org/about-cancer/stomach-cancer/survival
(https://www.cancerresearchuk.org/about-cancer/stomach-cancer/survival) .
Accessed May 2023.

7.   World Health Organisation. World Cancer Fact Sheet. Available at:
https://gco.iarc.fr/today/data/factsheets/populations/900-world-fact-sheets.pdf
(https://gco.iarc.fr/today/data/factsheets/populations/900-world-fact-sheets.pdf)
. Accessed May 2023.

 

 

Adrian Kemp

Company Secretary

AstraZeneca PLC

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