REG - AstraZeneca PLC - Imfinzi approved in EU for biliary tract cancer

AstraZenecaAnnouncement

21/12/2022 07:00

For best results when printing this announcement, please click on link below:
http://newsfile.refinitiv.com/getnewsfile/v1/story?guid=urn:newsml:reuters.com:20221221:nRSU3923Ka&default-theme=true

RNS Number : 3923K  AstraZeneca PLC  21 December 2022

21 December 2022 07:00 GMT

 

Imfinzi plus chemotherapy approved in the EU as first immunotherapy

regimen for patients with advanced biliary tract cancer

 

Approval based on TOPAZ-1 updated survival results showing Imfinzi

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

 

AstraZeneca's Imfinzi (durvalumab) has been approved 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 approval by the European Commission was based 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)
. The approval follows the recommendation
(https://www.astrazeneca.com/media-centre/press-releases/2022/imfinzi-plus-chemotherapy-recommended-for-approval-in-the-eu-by-chmp-as-first-immunotherapy-regimen-for-advanced-biliary-tract-cancer.html)
by The Committee for Medicinal Products for Human Use of the European
Medicines Agency in November 2022.

 

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 (based on a hazard ratio  HR  of 0.80; 95% confidence
interval  CI  0.66-0.97; p=0.021). Updated results 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 treated with Imfinzi plus chemotherapy 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
(cholangiocarcinoma) and gallbladder.(1,2) There are approximately 211,000 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 and The Christie NHS Foundation Trust, UK, and a lead investigator
in the TOPAZ-1 Phase III trial, said: "Today's approval marks an important
shift in the treatment of this aggressive and often overlooked disease and a
significant improvement compared to standard of care for these patients. After
waiting over a decade for new therapeutic options, biliary tract cancer
patients in the EU will now have the opportunity to benefit from an
immunotherapy-based treatment for the first time."

 

Dave Fredrickson, Executive Vice President, Oncology Business Unit,
AstraZeneca, said: "With this approval, Imfinzi plus chemotherapy becomes the
only immunotherapy-based treatment option available to patients in the EU with
advanced biliary tract cancer. This approval underscores our commitment to
transform survival outcomes while addressing the high unmet need for new and
improved treatments for patients with hepatobiliary cancers."

 

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 plus
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 and other countries for the treatment of adults 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 was 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 was 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 the only approved immunotherapy in unresectable or metastatic BTC,
unresectable hepatocellular carcinoma [in combination with Imjudo
(tremelimumab)], and the curative-intent setting of unresectable, Stage III
non-small cell lung cancer (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 in the US, EU, Japan, China and many other countries
around the world for the treatment of extensive-stage small cell lung cancer
(ES-SCLC) based on the CASPIAN Phase III trial. In 2021, updated results from
the CASPIAN trial showed Imfinzi plus chemotherapy tripled patient survival at
three years versus chemotherapy alone.

 

Imfinzi is also approved in the US for the treatment of adult patients with
Stage IV (metastatic) NSCLC in combination with Imjudo and chemotherapy.

 

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 in combination with chemotherapy (gemcitabine
plus cisplatin) for advanced BTC and in combination with Imjudo 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 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 in
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 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)
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 December 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 December 2022.

 

Adrian Kemp

Company Secretary

AstraZeneca PLC

This information is provided by RNS, the news service of the London Stock Exchange. RNS is approved by the Financial Conduct Authority to act as a Primary Information Provider in the United Kingdom. Terms and conditions relating to the use and distribution of this information may apply. For further information, please contact
rns@lseg.com (mailto:rns@lseg.com)
 or visit
www.rns.com (http://www.rns.com/)
.

RNS may use your IP address to confirm compliance with the terms and conditions, to analyse how you engage with the information contained in this communication, and to share such analysis on an anonymised basis with others as part of our commercial services. For further information about how RNS and the London Stock Exchange use the personal data you provide us, please see our
Privacy Policy (https://www.lseg.com/privacy-and-cookie-policy)
.   END  MSCBKKBBCBDDNBB