REG - AstraZeneca PLC - Imfinzi combination improves PFS in liver cancer

AstraZenecaAnnouncement

09/11/2023 07:15

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RNS Number : 8660S  AstraZeneca PLC  09 November 2023

09 November 2023

 

Imfinzi plus bevacizumab met primary endpoint for progression-free survival in
liver cancer eligible for embolisation in EMERALD-1 Phase III trial

 

First global Phase III trial to show improved clinical outcome for systemic
therapy

in combination with transarterial chemoembolisation (TACE) in this setting

 

Positive high-level results from the EMERALD-1 Phase III trial showed
AstraZeneca's Imfinzi (durvalumab) in combination with transarterial
chemoembolisation (TACE) and bevacizumab demonstrated a statistically
significant and clinically meaningful improvement in the primary endpoint of
progression-free survival (PFS) versus TACE alone in patients with
hepatocellular carcinoma (HCC) eligible for embolisation. The trial continues
to follow the secondary endpoint of overall survival (OS).

 

Liver cancer, of which HCC is the most common type, is the third-leading cause
of cancer death with an estimated 900,000 people worldwide diagnosed each
year.(1,2) Approximately 20-30% of patients are eligible for embolisation, a
procedure that blocks the blood supply to the tumour and can also deliver
chemotherapy or radiation therapy directly to the liver.(3-9) Despite being
the standard of care in this setting, most patients who receive embolisation
experience rapid disease progression or recurrence.(10-14)

 

Dr. Riccardo Lencioni, Professor and Director of the Cancer Imaging Program in
the Department of Diagnostic and Interventional Radiology of Pisa University
Hospital in Pisa, Italy, and principal investigator in the trial, said:
"Patients with liver cancer eligible for embolisation experience high rates of
progression or recurrence and do not have the opportunity for early
intervention with effective systemic therapy. These results for durvalumab
plus bevacizumab have the potential to reshape the treatment of this complex
disease with a poor prognosis by showing for the first time that adding an
immunotherapy combination to TACE significantly improves progression-free
survival."

 

Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca,
said: "These positive results for Imfinzi-based treatment in EMERALD-1 may
bring the potential of immunotherapy to patients with earlier stages of liver
cancer. We look forward to discussing these data with regulatory authorities
and seeing the survival data mature over time, which will be important as we
aim to bring this novel treatment option to patients."

 

The safety profiles for Imfinzi and TACE plus bevacizumab were consistent with
the known profile of each medicine, and there were no new safety findings.

 

The data will be presented at a forthcoming medical meeting and shared with
regulatory authorities.

 

AstraZeneca has an extensive clinical development programme further assessing
Imfinzi across multiple gastrointestinal (GI) cancer settings, including in
combination with bevacizumab in adjuvant HCC (EMERALD-2) and in combination
with Imjudo (tremelimumab), lenvatinib and TACE in embolisation-eligible HCC
(EMERALD-3).

 

Notes

 

Liver cancer

Liver cancer is the third-leading cause of cancer death and the sixth most
commonly diagnosed cancer worldwide.(1-2) Asia holds more than 70% of the
world's new liver cancer cases.(15) About 75% of all primary liver cancers in
adults are HCC.(1) Between 80-90% of all patients with HCC also have
cirrhosis.(16) Chronic liver diseases such as cirrhosis are associated with
inflammation that over time can lead to the development of HCC.(16)
Immunotherapy is a proven treatment modality in HCC with approved options
available for patients in later-line settings.(17)

 

EMERALD-1

EMERALD-1 is a randomised, double-blind, placebo-controlled, multicentre,
global Phase III trial of Imfinzi plus TACE concurrently, followed by Imfinzi
with or without bevacizumab until progression versus TACE alone in a total of
616 patients with unresectable HCC eligible for embolisation.

 

The trial was conducted in 157 centres across 18 countries, including in North
America, Australia, Europe, South America and Asia. The primary endpoint was
PFS for Imfinzi and TACE plus bevacizumab versus TACE alone, and secondary
endpoints include PFS for Imfinzi plus TACE, overall survival,
patient-reported outcomes and objective response rate.

 

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 HCC in the US, EU,
Japan and many other countries based on the TOPAZ-1 and HIMALAYA Phase III
trials, respectively.

 

In addition to its indications in 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 2023, AstraZeneca announced
positive results for Phase III trials including combinations with Imfinzi in
ovarian (DUO-O) and endometrial (DUO-E) cancers, as well as in resectable
NSCLC (AEGEAN).

 

In addition to the EMERALD programme across multiple liver cancer settings,
AstraZeneca has ongoing registrational trials investigating Imfinzi in
resectable gastric and gastroesophageal junction cancers (MATTERHORN) and in
locally advanced oesophageal cancer (KUNLUN). In June 2023, Imfinzi added to
standard-of-care neoadjuvant chemotherapy met a key secondary endpoint of
pathologic complete response in the MATTERHORN Phase III trial.

 

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.(18)

 

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 AZD0901. AZD0901 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 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.   ASCO. Liver Cancer: View All Pages. Available at:
https://www.cancer.net/cancer-types/liver-cancer/view-all.
Accessed November 2023.

2.   WHO. Liver Cancer Fact Sheet. Available at:
https://gco.iarc.fr/today/data/factsheets/cancers/11-Liver-fact-sheet.pdf.
Accessed November 2023.

3.   Lin Y-J, et al. Treatment patterns and survival in hepatocellular
carcinoma in the United States and Taiwan. PLoS ONE. 2020;15(10):e0240542.

4.   Park J-W, et al. Global patterns of hepatocellular carcinoma management
from diagnosis to death: the BRIDGE Study. Liver Int. 2015;35(9):2155-2166.

5.   Henriksson M, et al. Treatment patterns and survival in patients with
hepatocellular carcinoma in the Swedish national registry SweLiv. BJS Open.
2020;4(1):109-117.

6.   Wehling C, et al. Treatment stage migration and treatment sequences in
patients with hepatocellular carcinoma: drawbacks and opportunities. J Cancer
Res Clin Oncol. 2021;147(8):2471-2481.

7.   Fukuda H, et al. Differences in healthcare expenditure estimates
according to statistical approach: A nationwide claims database study on
patients with hepatocellular carcinoma. PLoS ONE. 2020;15(8):e0237316.

8.   Akada K, et al. Database analysis of patients with hepatocellular
carcinoma and treatment flow in early and advanced stages. Pharmacol Res
Perspect. 2019;7(4):e00486.

9.   Chon YE, et al. Hepatocellular Carcinoma in Korea between 2012 and
2014: an Analysis of Data from the Korean Nationwide Cancer Registry. J Liver
Cancer. 2020;20(2):135-147.

10.  Cerban R, et al. Predictive Factors of Tumor Recurrence and Survival in
Patients with Hepatocellular Carcinoma treated with Transarterial
Chemoembolization. J Gastrointestin Liver Dis. 2018 Dec;27(4):409-417.

11.  Lencioni R, et al. Sorafenib or placebo plus TACE with
doxorubicin-eluting beads for intermediate stage HCC: The SPACE trial. J
Hepatol. 2016 May;64(5):1090-1098.

12.  Golfieri R, et al. Hepatocellular carcinoma responding to superselective
transarterial chemoembolization: an issue of nodule dimension? J Vasc Interv
Radiol. Apr;24(4):509-17.

13.  Kudo M, et al. Brivanib as adjuvant therapy to transarterial
chemoembolization in patients with hepatocellular carcinoma: A randomized
phase III trial. Hepatology. v;60(5):1697-707.

14.  Lencioni R, et al. Lipiodol transarterial chemoembolization for
hepatocellular carcinoma: A systematic review of efficacy and safety data.
Hepatology, 2016;64: 106-116.

15.  Liu Y, et al. Changes in the Epidemiology of Hepatocellular Carcinoma in
Asia. Cancers (Basel). 2022;14(18):4473.

16.  Tarao K, et al. Real impact of liver cirrhosis on the development of
hepatocellular carcinoma in various liver diseases-meta‐analytic assessment.
Cancer Med. 2019;8(3):1054-1065.

17.  Colagrande S, et al. Challenges of advanced hepatocellular
carcinoma. World J Gastroenterol. 2016;22(34):7645-7659.

18.  World Health Organisation. World Fact Sheet. Available at:
https://gco.iarc.fr/today/data/factsheets/populations/900-world-fact-sheets.pdf.
Accessed November 2023.

 

Adrian Kemp

Company Secretary

AstraZeneca PLC

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