FORM 6-K
SECURITIES
AND EXCHANGE COMMISSION
Washington,
D.C. 20549
Report
of Foreign Issuer
Pursuant
to Rule 13a-16 or 15d-16 of
the
Securities Exchange Act of 1934
For the
month of October 2021
Commission
File Number: 001-11960
AstraZeneca PLC
1
Francis Crick Avenue
Cambridge
Biomedical Campus
Cambridge
CB2 0AA
United
Kingdom
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82-_____________
AstraZeneca
PLC
INDEX
TO EXHIBITS
1.
Imfinzi &
tremelimumab improved OS in liver cancer
15 October 2021 7:00 BST
Imfinzi plus tremelimumab significantly improved
overall survival in HIMALAYA Phase III trial in 1st-line
unresectable liver cancer
Trial met primary endpoint of overall survival with a single
priming
dose of tremelimumab plus Imfinzi every four weeks vs.
sorafenib
Imfinzi monotherapy met the overall survival endpoint of
non-inferiority vs. sorafenib
Positive high-level results from the HIMALAYA Phase III trial
showed a single, high priming dose of tremelimumab added
to Imfinzi (durvalumab) demonstrated a statistically
significant and clinically meaningful overall survival (OS) benefit
versus sorafenib as a 1st-line treatment for patients
with unresectable hepatocellular carcinoma
(HCC) who
had not received prior systemic therapy and were not eligible for
localised treatment. This novel dose and schedule of
tremelimumab, an anti-CTLA4 antibody, and Imfinzi is called the STRIDE regimen (Single
Tremelimumab Regular Interval Durvalumab). The combination
demonstrated a favourable safety profile, and the addition of
tremelimumab to Imfinzi did not increase severe hepatic
toxicity.
Imfinzi alone demonstrated
non-inferior OS to sorafenib with a numerical trend in favour
of Imfinzi and an improved tolerability profile
compared to sorafenib.
Liver cancer, of which HCC is the most common type, is the
third leading cause of cancer death and the sixth most commonly
diagnosed cancer worldwide with approximately 900,000 people
diagnosed each year.1-2 Only
7% of patients with advanced disease survive five
years.3
Ghassan Abou-Alfa, MD, MBA, Attending Physician at Memorial Sloan
Kettering Cancer Center and principal investigator in the HIMALAYA
Phase III trial, said: "HIMALAYA is the first Phase III trial
to add a novel single priming dose of an anti-CTLA4 antibody to
another checkpoint inhibitor, durvalumab. This serves to boost the
patient's own immune system against their liver cancer, aiming to
maximise long-term survival with minimal side effects. This is very
exciting news for our patients."
Susan Galbraith, Executive Vice President, Oncology R&D,
AstraZeneca, said: "Inhibition of CTLA-4 has shown the ability to
drive benefit particularly in the tail of the survival curve in
several settings. This is the first time a dual immunotherapy
regimen has improved overall survival as a 1st-line treatment for
patients with unresectable liver cancer for whom treatment options
are limited and long-term outcomes are poor."
The data from the HIMALAYA Phase III trial will be presented at a
forthcoming medical meeting.
Imfinzi and tremelimumab
were granted Orphan Drug Designations in the US for the treatment
of HCC in 2020. Tremelimumab was also granted orphan designation in
the EU in HCC in 2020.
Notes
Liver cancer
About 75% of all primary liver cancers are HCC.1 Between
80-90% of all patients with HCC also have cirrhosis, which is
primarily caused by infection with the hepatitis B or C
viruses.4 Chronic
liver diseases are associated with inflammation that, over time,
results in immunosuppression and can lead to the development of
HCC.4,5
The unique immune environment of liver cancer provides clear
rationale for researching medicines that harness the power of the
immune system to treat HCC.6 A
critical unmet need exists for patients with HCC who face limited
treatment options.6 More
than half of patients are diagnosed at advanced stages of the
disease, often when symptoms first appear.6
HIMALAYA
HIMALAYA was a randomised, open-label, multicentre, global Phase
III trial of Imfinzi monotherapy and the STRIDE regimen,
comprising a single priming dose of tremelimumab 300mg added
to Imfinzi 1500mg followed by Imfinzi every four weeks versus sorafenib, a
standard-of-care multi-kinase inhibitor, in a total of 1,324
patients with unresectable, advanced HCC who had not been treated
with prior systemic therapy and were not eligible for locoregional
therapy (treatment localised to the liver and surrounding
tissue).
The trial was conducted in 190 centres across 16 countries,
including in the US, Canada, Europe, South America and Asia. The
primary endpoint was OS for STRIDE versus sorafenib and key
secondary endpoints included OS for Imfinzi versus sorafenib, objective response rate
and progression-free survival (PFS) for STRIDE and
for Imfinzi alone.
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.
In 1st-line Stage IV NSCLC, positive results from the POSEIDON
Phase III trial showed Imfinzi plus chemotherapy with a short course of
tremelimumab 75mg demonstrated a statistically significant and
clinically meaningful improvement in OS and PFS compared to
chemotherapy.
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
NSCLC, SCLC, bladder cancer, HCC, biliary tract cancer (BTC),
oesophageal cancer, gastric and gastroesophageal cancer, cervical
cancer, ovarian cancer, endometrial cancer, and other solid
tumours.
Tremelimumab
Tremelimumab is a human monoclonal antibody and potential new
medicine that targets the activity of cytotoxic
T-lymphocyte-associated protein 4 (CTLA-4). Tremelimumab blocks the
activity of CTLA-4, contributing to T-cell activation, priming the
immune response to cancer and fostering cancer cell
death.
Tremelimumab is being tested in a clinical trial programme in
combination with Imfinzi in NSCLC, SCLC, bladder cancer and liver
cancer.
AstraZeneca in gastrointestinal cancers
AstraZeneca has a broad development programme for the treatment of
gastrointestinal (GI) cancers across several medicines spanning a
variety of tumour types and stages of disease. In 2020, GI cancers
collectively represented approximately 5.1 million new diagnoses
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 (durvalumab) is
being assessed in combinations including with tremelimumab in HCC,
BTC, oesophageal and gastric cancers in an extensive development
programme spanning early to late-stage disease across
settings.
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.2 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, small, targeted 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 and
follow the Company on Twitter @AstraZeneca.
Contacts
For details on how to contact the Investor Relations Team, please
click here.
For Media contacts, click here.
References
1.
ASCO. Liver Cancer: View All
Pages. Available at: https://www.cancer.net/cancer-types/liver-cancer/view-all.
Accessed October 2021.
2.
WHO. Liver Cancer Fact Sheet.
Available at: https://gco.iarc.fr/today/data/factsheets/cancers/11-Liver-fact-sheet.pdf.
Accessed October 2021.
3.
Sayiner M, et al. Disease Burden of Hepatocellular
Carcinoma: A Global Perspective. Digestive Diseases and
Sciences. 2019; 64:
910-917.
4.
Tarao K, et al. Real impact of liver cirrhosis on
the development of hepatocellular carcinoma in various liver
diseases-meta‐analytic
assessment. Cancer Med. 2019; 8(3): 1054-1065.
5.
Yu LX, et al. Role of nonresolving inflammation in
hepatocellular carcinoma development and
progression. Precision
Oncology. 2018:
2(8).
6.
Colagrande S, et al. Challenges of advanced
hepatocellular carcinoma. World J
Gastroenterol. 2016; 22(34):
7645-7659.
7.
WHO. World Cancer Fact Sheet.
Available at: https://gco.iarc.fr/today/data/factsheets/populations/900-world-fact-sheets.pdf.
Accessed October 2021.
Adrian Kemp
Company Secretary
AstraZeneca PLC
SIGNATURES
Pursuant
to the requirements of the Securities Exchange Act of 1934, the
Registrant has duly caused this report to be signed on its behalf
by the undersigned, thereunto duly authorized.
Date:
15 October 2021
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By: /s/
Adrian Kemp
|
|
Name:
Adrian Kemp
|
|
Title:
Company Secretary
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