REG - AstraZeneca PLC - Imfinzi combo granted Priority Review for BTC

AstraZenecaAnnouncement

04/05/2022 07:00

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RNS Number : 1936K  AstraZeneca PLC  04 May 2022

4 May 2022 07:00 BST

 

Imfinzi plus chemotherapy granted Priority Review in the US for patients

with locally advanced or metastatic biliary tract cancer

based on TOPAZ-1 Phase III trial

 

First Phase III trial in this setting to show improved overall survival with
an

immunotherapy added to chemotherapy over standard-of-care chemotherapy alone

 

AstraZeneca's supplemental Biologics License Application (sBLA)
for Imfinzi (durvalumab), in combination with standard-of-care chemotherapy,
has been accepted and granted Priority Review in the US for patients with
locally advanced or metastatic biliary tract cancer (BTC).

 

The Food and Drug Administration (FDA) grants Priority Review to applications
for medicines that, if approved, would offer significant improvements over
available options by demonstrating safety or efficacy improvements, preventing
serious conditions, or enhancing patient compliance.(1) The Prescription Drug
User Fee Act date, the FDA action date for their regulatory decision, is
during the third quarter of 2022.

 

BTC is a group of rare and aggressive cancers that occur in the bile ducts and
gallbladder. (2,3) Approximately 23,000 people in the US are diagnosed with
BTC each year.(2) These patients have a poor prognosis, with approximately 5%
to 15% of patients with BTC surviving five years.(4)

 

Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca,
said: "People with advanced biliary tract cancer have faced poor outcomes and
limited treatment options for too long, and today's news for the TOPAZ-1 trial
underscores the urgency to deliver new, effective therapies in this setting.
We are working closely with the FDA to bring the first immunotherapy-based
option to patients with this devastating cancer and potentially set a new
standard of care with Imfinzi plus chemotherapy."

 

The sBLA was based on results from an interim analysis of the TOPAZ-1 Phase
III trial presented
(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)
during the 2022 American Society of Clinical Oncology Gastrointestinal Cancers
(ASCO GI) Symposium. The data showed Imfinzi plus chemotherapy (gemcitabine
plus cisplatin) 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; 2-sided p=0.021). An estimated one in four (25%) patients treated
with Imfinzi plus chemotherapy were alive at two years compared to one in 10
(10%) treated with chemotherapy alone.

 

Results also showed a statistically significant 25% reduction in the risk of
disease progression or death with Imfinzi plus chemotherapy (HR, 0.75; 95% CI,
0.64-0.89; 2-sided p=0.001). The Imfinzi combination was generally well
tolerated and did not increase the discontinuation rate due to adverse events
compared to chemotherapy alone.

 

In December 2020, Imfinzi was granted Orphan Drug Designation in the US for
the treatment of BTC.

 

Notes

 

Biliary tract cancer

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).(2,3)

 

Cholangiocarcinoma is more common in China and South-East Asia and is on the
rise in Western countries.(2,4) 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.(4-6)

 

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.

 

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 small cell lung cancer (SCLC), NSCLC, bladder cancer, several GI cancers,
ovarian cancer, endometrial cancer, and other solid tumours.

 

In the past year, 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
contacts, click here (https://www.astrazeneca.com/media-centre/contacts.html)
.

 

References

1. FDA. Priority Review. Available at:
https://www.fda.gov/patients/fast-track-breakthrough-therapy-accelerated-approval-priority-review/priority-review.
Accessed May 2022.

2. Marcano-Bonilla L, et al. Biliary tract cancers: epidemiology, molecular
pathogenesis and genetic risk associations. CCO. 2016;5(5).

3. 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 May 2022.

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.

 

Adrian Kemp

Company Secretary

AstraZeneca PLC

 

 

 

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