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

AstraZenecaAnnouncement

05/09/2022 07:00

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RNS Number : 1907Y  AstraZeneca PLC  05 September 2022

5 September 2022 07:00 BST

 

Imfinzi plus chemotherapy approved in the US as the first immunotherapy
regimen for patients with advanced biliary tract cancer

 

Approval based on TOPAZ-1 Phase III trial results, which showed Imfinzi

combination reduced risk of death by 20% vs. chemotherapy alone

 

AstraZeneca's Imfinzi (durvalumab) has been approved in the US for the
treatment of adult patients with locally advanced or metastatic biliary tract
cancer (BTC) in combination with chemotherapy (gemcitabine plus cisplatin).

 

The approval by the Food and Drug Administration (FDA) was based on the
results from the TOPAZ-1 Phase III trial
(https://www.astrazeneca.com/content/astraz/media-centre/press-releases/2022/imfinzi-plus-chemotherapy-reduced-risk-of-death-by-20-in-1st-line-advanced-biliary-tract-cancer.html)
. In an interim analysis of TOPAZ-1, 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). An estimated one in four (25%)
patients treated with Imfinzi plus chemotherapy were still alive at two years
compared to one in 10 (10%) treated with chemotherapy alone. Results were
consistent across all prespecified subgroups, regardless of PD-L1 expression
or tumour location.

 

BTC is a group of rare and aggressive cancers that occur in the bile ducts and
gallbladder.(1,2) Approximately 23,000 people in the US are diagnosed with BTC
each year.(1) These patients have a poor prognosis, with approximately 5% to
15% of patients with BTC surviving five years.(3)

 

Aiwu Ruth He, MD, PhD, Associate Professor of Medicine, Leader of the GI
Cancer Program, Georgetown Lombardi Comprehensive Cancer Center, Medstar
Georgetown University Hospital, Washington DC, and a lead investigator in the
TOPAZ-1 Phase III trial, said: "This approval represents a major step forward
for patients with advanced biliary tract cancer, who urgently need new,
well-tolerated and effective treatment options after more than a decade of
limited innovation. The combination of durvalumab and chemotherapy should
become a new standard of care in this setting, having demonstrated
significantly improved survival for these patients who have historically faced
a poor prognosis."

 

Dave Fredrickson, Executive Vice President, Oncology Business Unit,
AstraZeneca, said: "For the first time, patients in the US with advanced
biliary tract cancer have an immunotherapy-based treatment option that
meaningfully extends survival and is well-tolerated. This approval for Imfinzi
and chemotherapy advances our ambition to challenge treatment expectations and
transform care for patients with gastrointestinal cancers with high unmet
need."

 

Stacie Lindsey, CEO, Cholangiocarcinoma Foundation, said: "Patients have been
waiting a long time for a new, first-line treatment option for biliary tract
cancer. The Foundation congratulates AstraZeneca for engaging in rare cancer
research, which impacts patients and families nationwide. We are especially
grateful to the patients who participated in this trial making it possible for
the broader rare disease community to benefit from this treatment."

 

The TOPAZ-1 Phase III trial results were presented at the 2022 American
Society of Clinical Oncology Gastrointestinal Cancers (ASCO GI) Symposium and
published in the New England Journal of Medicine Evidence
(https://evidence.nejm.org/doi/full/10.1056/EVIDoa2200015) . Imfinzi plus
chemotherapy was generally well tolerated and did not increase the
discontinuation rate due to adverse events compared to chemotherapy alone.

 

In July 2022, Imfinzi plus chemotherapy was added to the NCCN Clinical
Practice Guidelines in Oncology (NCCN Guidelines(®)) as a Category 1
preferred regimen as 1st-line therapy for locally advanced or metastatic BTC
based on the data from TOPAZ-1.(4)

 

The US regulatory submission for TOPAZ-1 was reviewed under Project Orbis,
which provides a framework for concurrent submission and review of oncology
medicines among participating international partners. As part of Project
Orbis, Imfinzi plus chemotherapy is also under regulatory review for the same
indication by the Australian Therapeutic Goods Administration, the Brazilian
Health Regulatory Agency (ANVISA), Health Canada, Israel's Ministry of Health
Pharmaceutical Administration, Singapore's Health Sciences Authority,
Switzerland's Swissmedic and the UK's Medicines and Healthcare products
Regulatory Agency.

 

The approval was granted after securing Priority Review
(https://www.astrazeneca.com/media-centre/press-releases/2022/imfinzi-combo-granted-priority-review-for-btc.html)
and Orphan Drug Designation for Imfinzi in the US in this setting. Regulatory
applications are also currently under review in Europe, 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)

 

Cholangiocarcinoma is more common in China and South-East Asia and is on the
rise in Western countries.(1,3) Gallbladder cancer is more common in certain
regions of South America, India and Japan.(5)

 

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.(3,5,6)

 

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.

 

In addition to the approval in BTC, Imfinzi is the only approved immunotherapy
in the curative-intent setting of unresectable, Stage III non-small cell lung
cancer (NSCLC) in patients whose disease has not progressed after
chemoradiotherapy and 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 for previously treated patients with advanced bladder
cancer in several countries.

 

Since the first approval in May 2017, more than 100,000 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.

 

Imfinzi combinations have demonstrated clinical benefit in multiple additional
cancer settings with positive Phase III trials in unresectable advanced liver
cancer (HIMALAYA) and metastatic NSCLC (POSEIDON).

 

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.(6)

 

Within this programme, the Company is committed to improving outcomes in
gastric, liver, BTC, oesophageal, pancreatic, and colorectal cancers.

 

Imfinzi is being assessed in combinations in liver, BTC, oesophageal and
gastric cancers in an extensive development programme spanning early to
late-stage disease.

 

The Company aims to understand the potential of Enhertu (trastuzumab
deruxtecan), a HER2-directed antibody drug conjugate, in the two most common
GI cancers, colorectal and gastric cancers. Enhertu is jointly developed and
commercialised by AstraZeneca and Daiichi Sankyo.

 

Lynparza (olaparib) is a first-in-class PARP inhibitor with a broad and
advanced clinical trial programme across multiple GI tumour types including
pancreatic and colorectal cancers. Lynparza is developed and commercialised in
collaboration with MSD (Merck & Co., Inc. inside the US and Canada).

 

AstraZeneca in immunotherapy

Immunotherapy is a therapeutic approach designed to stimulate the body's
immune system to attack tumours. The Company's Immuno-Oncology (IO) portfolio
is anchored in immunotherapies that have been designed to overcome evasion of
the anti-tumour immune response. AstraZeneca is invested in using IO
approaches that deliver long-term survival for new groups of patients across
tumour types.

 

The Company is pursuing a comprehensive clinical-trial programme that includes
Imfinzi as a single treatment and in combination with tremelimumab and other
novel antibodies in multiple tumour types, stages of disease, and lines of
treatment, and where relevant using the PD-L1 biomarker as a decision-making
tool to define the best potential treatment path for a patient.

 

In addition, the ability to combine the IO portfolio with radiation,
chemotherapy, and targeted small molecules from across AstraZeneca's oncology
pipeline, and from research partners, may provide new treatment options across
a broad range of tumours.

 

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
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.

 

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 September 2022.

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

4.   Referenced with permission from the NCCN Clinical Practice Guidelines
in Oncology (NCCN Guidelines®) for Breast Cancer V2.2022. © National
Comprehensive Cancer Network, Inc. 2022. All rights reserved. Accessed
September 2022. To view the most recent and complete version of the guideline,
go online to NCCN.org. NCCN makes no warranties of any kind whatsoever
regarding their content, use or application and disclaims any responsibility
for their application or use in any way.

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.

 

 

Adrian Kemp

Company Secretary

AstraZeneca PLC

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