REG - AstraZeneca PLC - Imfinzi improves survival in biliary tract cancer

AstraZenecaAnnouncement

19/01/2022 07:10

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RNS Number : 8834Y  AstraZeneca PLC  19 January 2022

19 January 2022 07:05 GMT

 

Imfinzi plus chemotherapy reduced risk of death by 20% in 1st-line advanced
biliary tract cancer

 

TOPAZ-1 is the first Phase III trial to show improved survival

with an immunotherapy combination in this setting

 

Combination did not increase discontinuations due to adverse events vs.
chemotherapy alone

 

Positive results from the TOPAZ-1 Phase III trial showed AstraZeneca's Imfinzi
(durvalumab), in combination with standard-of-care chemotherapy, demonstrated
a statistically significant and clinically meaningful improvement in overall
survival (OS) and progression-free survival (PFS) versus chemotherapy alone as
a 1st-line treatment for patients with advanced biliary tract cancer (BTC).

 

These results will be presented on 21 January at the 2022 American Society of
Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium.

 

BTC is a group of rare and aggressive cancers that occur in the bile ducts and
gallbladder.(1,2)  Approximately 50,000 people in the US, Europe and Japan
and about 210,000 people worldwide are diagnosed with BTC each year.(3-5)
These patients have a poor prognosis, with approximately 5% to 15% of all
patients with BTC surviving five years.(6)

 

Do-Youn Oh, MD, PhD, Professor, Division of Medical Oncology, Department of
Internal Medicine at Seoul National University Hospital and Seoul National
University College of Medicine, and principal investigator in the TOPAZ-1
Phase III trial, said: "After minimal progress for more than a decade in
advanced biliary tract cancer, the TOPAZ-1 results are a tremendous advance
for our patients, showing a clear survival benefit for Imfinzi added to
chemotherapy compared to standard of care with a remarkable safety profile.
This combination will provide a desperately needed and potentially
practice-changing new treatment option in a setting where the current
prognosis is devastating."

 

Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca,
said: "The results from the TOPAZ-1 trial challenge treatment expectations in
advanced biliary tract cancer and provide compelling evidence that longer-term
survival is possible. Overall survival improves over time with an estimated
one in four patients on Imfinzi plus chemotherapy alive at two years compared
to one in ten on chemotherapy alone. This is a potential new standard of care
for patients in this setting and we remain committed to making advances in
gastrointestinal cancers with high unmet need."

 

In a predefined interim analysis, patients treated with Imfinzi in combination
with standard-of-care chemotherapy experienced a 20% reduction in the risk of
death 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). Median OS was 12.8
months versus 11.5 for chemotherapy. An estimated 25% of patients were still
alive at two years versus 10% for chemotherapy.

 

Results also showed a 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). Median PFS was 7.2 months for the combination versus 5.7 for
chemotherapy. Patients treated with Imfinzi plus chemotherapy achieved an
objective response rate (ORR) of 26.7% versus an ORR of 18.7% for patients
treated with chemotherapy alone.

 

Summary of efficacy results(i):

                                    Imfinzi + chemotherapy  Placebo + chemotherapy

                                    (n=341)                 (n=344)
 OS(ii,iii)
 Percentage of patients with event  58.1                    65.7
 Median OS (95% CI) (in months)     12.8 (11.1, 14.0)       11.5 (10.1, 12.5)
 HR (95% CI)                        0.80 (0.66, 0.97)

 2-sided p-value                    0.021
 OS rate at 18 months (95% CI) (%)  35.1 (29.1, 41.2)       25.6 (19.9, 31.7)
 OS rate at 24 months (95% CI) (%)  24.9 (17.9, 32.5)       10.4 (4.7, 18.8)
 PFS(iv,v)
 Percentage of patients with event  80.9                    86.3
 Median PFS (95% CI) (in months)    7.2 (6.7, 7.4)          5.7 (5.6, 6.7)
 HR (95% CI)                        0.75 (0.64, 0.89)

 2-sided p-value                    0.001
 ORR (%)                            26.7                    18.7

i. Analysis was done at 62% maturity in OS data.

ii.          Investigator-assessed OS data cut-off date was 11 August
2021.

iii.         Median follow-up in censored patients at DCO: 13.7 months
(range 0.4-27.2) for Imfinzi plus chemotherapy, 12.6 months (range 0.7-26.0)
for chemotherapy alone.

iv.         Investigator-assessed PFS data cut-off date was 11 August
2021.

v.          Median follow-up in censored patients at DCO: 9.2 months
(range 0.0-24.0) for Imfinzi plus chemotherapy, 6.9 months (range 0.0-20.4)
for chemotherapy alone.

 

Imfinzi plus chemotherapy 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 62.7% of patients treated with
Imfinzi and chemotherapy, and by 64.9% of patients receiving chemotherapy
alone. Treatment-related AEs led to discontinuation in 8.9% of patients
treated with the Imfinzi combination versus 11.4% of patients receiving
chemotherapy.

 

In December 2020, Imfinzi was granted Orphan Drug Designation in the US for
the treatment of BTC. In October 2021
(https://www.astrazeneca.com/media-centre/press-releases/2021/imfinzi-improved-survival-in-biliary-tract-cancer.html)
, an Independent Data Monitoring Committee recommended the TOPAZ-1 Phase III
trial to be unblinded at an interim analysis due to clear evidence of efficacy
for Imfinzi plus chemotherapy.

 

An additional presentation featured during the ASCO Gastrointestinal Cancers
Symposium will showcase Imfinzi data from the HIMALAYA Phase III trial,
demonstrating the potential of this medicine in the treatment of unresectable
liver cancer.

 

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).(1,2)

 

Cholangiocarcinoma is more common in China and Thailand and is on the rise in
Western countries.(1,6) Gallbladder cancer is more common in certain regions
of South America, India and Japan.(7)

 

Apart from ampullary cancer, early-stage BTC 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.(8-10)

 

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 (ampullary carcinoma was excluded).

 

The primary endpoint was OS 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 chemoradiation therapy, 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.

 

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, NSCLC, bladder cancer, several GI cancers,
cervical cancer, 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.(11)

 

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 colorectal and
gastric cancers - the two most common GI 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 anti-tumour
immune suppression. 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/) 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 January 2022.

3. Siegel R, et al. Cancer Statistics. CA Cancer J Clin. 2020; 70: 7-30.

4. Nakachi K, et al. A randomized Phase III trial of adjuvant S1 therapy vs.
observation alone in resected biliary tract cancer: Japan Clinical Oncology
Group Study (JCOG1202, ASCOT). Japanese Journal of Clinical Oncology. 2018;
48(4): 392-395.

5. GBD 2017 Disease and Injury Incidence and Prevalence Collaborators. Global,
regional, and national incidence, prevalence, and years lived with disability
for 354 diseases and injuries for 195 countries and territories, 1990-2017: a
systematic analysis for the Global Burden of Disease Study 2017. Lancet.
2018;392(10159):1789-1858.

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

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

8. Banales JM, et al. Cholangiocarcinoma 2020: the next horizon in mechanisms
and management. Nature Reviews Gastroenterology & Hepatology. 2020; 17:
557-588.

9. Mehrotra B. Gallbladder cancer: Epidemiology, risk factors, clinical
features, and diagnosis. Available at:
https://www.uptodate.com/contents/gallbladder-cancer-epidemiology-risk-factors-clinical-features-and-diagnosis.
Accessed January 2022.

10. He XD, et al. Association of metabolic syndromes and risk factors with
ampullary tumors development: A case-control study in China. World J
Gastroenterol. 2014; 20(28): 9541-9548.

11. WHO. World Cancer Fact Sheet. Available at:

https://gco.iarc.fr/today/data/factsheets/populations/900-world-fact-sheets.pdf.
Accessed January

2022.

 

Adrian Kemp

Company Secretary

AstraZeneca PLC

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