REG - AstraZeneca PLC - Imfinzi recommended for approval in the EU for BTC

AstraZenecaAnnouncement

14/11/2022 07:16

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RNS Number : 2234G  AstraZeneca PLC  14 November 2022

14 November 2022 07:05 GMT

 

Imfinzi plus chemotherapy recommended for approval in the EU by CHMP

as first immunotherapy regimen for advanced biliary tract cancer

 

Positive opinion based on TOPAZ-1 Phase III trial updated survival results
showing

Imfinzi combination reduced risk of death by 24% vs. chemotherapy alone

 

AstraZeneca's Imfinzi (durvalumab) has been recommended for marketing
authorisation in the European Union (EU) for the 1st-line treatment of adult
patients with unresectable or metastatic biliary tract cancer (BTC) in
combination with chemotherapy (gemcitabine plus cisplatin).

 

The Committee for Medicinal Products for Human Use (CHMP) of the European
Medicines Agency based its positive opinion on the primary results from the
TOPAZ-1 Phase III trial published in the New England Journal of Medicine
Evidence (https://evidence.nejm.org/doi/full/10.1056/EVIDoa2200015) , and on
the updated results presented at the European Society for Medical Oncology
Congress 2022
(https://www.astrazeneca.com/media-centre/press-releases/2022/imfinzi-plus-chemotherapy-further-improved-overall-survival-benefit-in-advanced-biliary-tract-cancer-in-the-topaz-1-phase-iii-trial.html)
.

 

At the interim analysis
(https://www.astrazeneca.com/media-centre/press-releases/2022/imfinzi-plus-chemotherapy-reduced-risk-of-death-by-20-in-1st-line-advanced-biliary-tract-cancer.html)
, Imfinzi plus chemotherapy reduced the risk of death by 20% versus
chemotherapy alone (hazard ratio  HR  0.80; 95% confidence interval  CI 
0.66-0.97; p=0.021).

Updated results
(https://www.astrazeneca.com/media-centre/press-releases/2022/imfinzi-plus-chemotherapy-further-improved-overall-survival-benefit-in-advanced-biliary-tract-cancer-in-the-topaz-1-phase-iii-trial.html)
from TOPAZ-1 after an additional 6.5 months of follow-up showed a 24%
reduction in the risk of death versus chemotherapy alone (HR 0.76; 95% CI,
0.64-0.91), with more than two times as many patients estimated to be alive at
two years versus chemotherapy alone (23.6% versus 11.5%). Updated median
overall survival (OS) was 12.9 months versus 11.3 with chemotherapy.

 

BTC is a group of rare and aggressive cancers that occur in the bile ducts and
gallbladder.(1,2) There are approximately 210,000 new patients diagnosed with
gallbladder and biliary tract cancer each year, and about 40,000 of these
occur across Europe.(3) These patients have a poor prognosis, with
approximately 5% to 15% of patients with BTC surviving five years.(4)

 

Juan W. Valle, MD, Professor of Medical Oncology at the University of
Manchester, UK, and a lead investigator in the TOPAZ-1 Phase III trial, said:
"This positive opinion is welcome news for patients with advanced biliary
tract cancer in the European Union who face a poor prognosis and limited
treatment options. The combination of durvalumab and chemotherapy is a
significant advance for patients after more than a decade of limited progress,
and this regimen should become a new standard of care option once approved."

 

Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca,
said: "If approved, Imfinzi plus chemotherapy will provide patients with
advanced biliary tract cancer the first opportunity for treatment with an
immunotherapy-based combination. This innovative regimen has been shown to
significantly prolong patients' lives, and we look forward to bringing this
option to those in the European Union as soon as possible."

 

Imfinzi plus chemotherapy was generally well tolerated, with no new safety
signals observed, and did not increase the discontinuation rate due to adverse
events (AEs) compared to chemotherapy alone. Grade 3 or 4 treatment-related
AEs were experienced by 60.9% of patients treated with Imfinzi and
chemotherapy, and by 63.5% of patients treated with chemotherapy alone.

 

Imfinzi plus chemotherapy is approved
(https://www.astrazeneca.com/content/astraz/media-centre/press-releases/2022/imfinzi-approved-in-us-for-biliary-tract-cancer.html#!)
in the US, Canada, South Korea and Brazil for the treatment of patients with
locally advanced or metastatic BTC. Regulatory applications are also currently
under review in Japan and several other countries based on the TOPAZ-1
results.

 

Notes

 

Biliary tract cancer

BTC is a group of rare and aggressive gastrointestinal (GI) cancers that form
in the cells of the bile ducts (cholangiocarcinoma), gallbladder or ampulla of
Vater (where the bile duct and pancreatic duct connect to the small
intestine).(1,2)

 

Early-stage BTC affecting the bile ducts and gallbladder often presents
without clear symptoms and most new cases of BTC are therefore diagnosed at an
advanced stage, when treatment options are limited and the prognosis is
poor.(4-6) Cholangiocarcinoma is more common in China and Southeast Asia and
is on the rise in Western countries.(1,)(4)

 

TOPAZ-1

TOPAZ-1 is a randomised, double-blind, placebo controlled, multicentre, global
Phase III trial of Imfinzi in combination with chemotherapy (gemcitabine plus
cisplatin) versus placebo in combination with chemotherapy as a 1st-line
treatment in 685 patients with unresectable advanced or metastatic BTC
including intrahepatic and extrahepatic cholangiocarcinoma, and gallbladder
cancer. Patients with ampullary carcinoma were excluded.

 

The primary endpoint is overall survival and key secondary endpoints included
progression-free survival, objective response rate and safety. The trial was
conducted in 105 centres across 17 countries including in the US, Europe,
South America and several countries in Asia including South Korea, Thailand,
Japan and China.

 

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 also the only approved immunotherapy in unresectable or metastatic
biliary tract cancer and hepatocellular carcinoma [in combination with Imjudo
(tremelimumab)]. It is also approved in combination with Imjudo and
chemotherapy in metastatic non-small cell lung cancer (NSCLC) and in the
curative-intent setting of unresectable, Stage III NSCLC in patients whose
disease has not progressed after chemoradiotherapy. It is the global standard
of care in this setting based on the PACIFIC Phase III trial.

 

Imfinzi is also approved for previously treated patients with advanced bladder
cancer in several countries.

 

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.

 

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.

 

Imfinzi is approved in the US and several other countries in combination with
chemotherapy (gemcitabine plus cisplatin) for advanced biliary tract cancer
and in the US in combination with Imjudo (tremelimumab) in unresectable
hepatocellular carcinoma. 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 in immuno-oncology (IO)

AstraZeneca 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)
and follow the Company on Twitter @AstraZeneca
(https://twitter.com/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.  Marcano-Bonilla L, et al. Biliary tract cancers: epidemiology, molecular
pathogenesis and genetic risk associations. CCO. 2016;5(5).

2.   ESMO. What is Biliary Tract Cancer. Available at:

https://www.esmo.org/content/download/266801/5310983/1/EN-Biliary-Tract-Cancer-Guide-for-Patients.pdf.
Accessed November 2022.

3.   Ouyang G, et al. The global, regional, and national burden of
gallbladder and biliary tract cancer and its attributable risk factors in 195
countries and territories, 1990 to 2017: A systematic analysis for the Global
Burden of Disease Study 2017. Cancer. 2021;127:2238-2250.

4.   Turkes F, et al. Contemporary Tailored Oncology Treatment of Biliary
Tract Cancers. Gastroenterol Res Pract. 2019;2019:7698786.

5.   Rawla P, et al. Epidemiology of gallbladder cancer. Clin Exp Hepatol.
2019;5(2):93-102.

6.   Banales JM, et al. Cholangiocarcinoma 2020: the next horizon in
mechanisms and management. Nat Rev Gastroenterol Hepatol. 2020;17:557-588.

7.   WHO. World Cancer Fact Sheet. Available at:
https://gco.iarc.fr/today/data/factsheets/populations/900-world-fact-sheets.pdf.
Accessed November 2022.

 

 

Adrian Kemp

Company Secretary

AstraZeneca PLC

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