a8908y
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 January 2022
Commission
File Number: 001-11960
AstraZeneca PLC
1
Francis Crick Avenue
Cambridge
Biomedical Campus
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United
Kingdom
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AstraZeneca PLC
INDEX
TO EXHIBITS
1.
Imfinzi
combo shows unprecedented survival in HCC
19 January 2022 07:00 GMT
Imfinzi plus tremelimumab demonstrated unprecedented
survival in 1st-line unresectable liver cancer with 31% of
patients alive at three years
A single priming dose of tremelimumab plus Imfinzi every
four
weeks reduced risk of death by 22% in HIMALAYA
Phase III trial
Combination also showed no increase in severe liver toxicity and
fewer
discontinuations due to treatment-related adverse events vs.
sorafenib
Positive results from the HIMALAYA Phase III trial showed a single
priming dose of tremelimumab added to Imfinzi (durvalumab) demonstrated a statistically
significant and clinically meaningful improvement in overall
survival (OS) 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 Imfinzi and tremelimumab, an anti-CTLA4 antibody, is
called the STRIDE regimen (Single Tremelimumab Regular Interval
Durvalumab). Results from the trial will be presented on 21
January at the 2022 American Society of Clinical Oncology (ASCO)
Gastrointestinal Cancers Symposium.
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.1,2 Approximately
80,000 people in the US, Europe and Japan and 260,000 people in
China present with advanced, unresectable HCC each
year.3 Only
7% of patients with advanced disease survive five
years.4
Ghassan Abou-Alfa, MD, MBA, Attending Physician at Memorial Sloan
Kettering Cancer Center and principal investigator in the HIMALAYA
Phase III trial, said: "Patients with unresectable liver cancer
face a dismal prognosis, and new treatment options are critical to
improving long-term survival. The three-year overall survival rate
and favourable safety profile seen with the STRIDE regimen set a
new benchmark in this setting and underscore the potential of this
innovative treatment approach."
Susan Galbraith, Executive Vice President, Oncology R&D,
AstraZeneca, said: "The HIMALAYA trial reinforces our scientific
approach for tremelimumab, tapping into the potential of CTLA-4
inhibition and a unique dosing regimen to prime the immune system
to help patients live longer and with minimal side effects. We look
forward to bringing potential new treatment options to patients
with unresectable liver cancer, an area of high unmet need, as
quickly as possible."
Patients treated with the STRIDE regimen experienced a 22%
reduction in the risk of death versus sorafenib (based on a hazard
ratio [HR] of 0.78, 96.02% confidence interval [CI] 0.65-0.93;
p=0.0035). Median OS was 16.4 months versus 13.8 for sorafenib. An
estimated 31% of patients were still alive at three years versus
20% for sorafenib.
Results also showed an increase in objective response rate (ORR)
with the STRIDE regimen versus sorafenib (20.1% vs. 5.1%). Median
duration of response (DoR) was 22.3 months with the STRIDE regimen
versus 18.4 with sorafenib. The addition of tremelimumab
to Imfinzi did not increase severe liver toxicity, and
no bleeding risk was observed.
HIMALAYA also tested Imfinzi monotherapy, which demonstrated non-inferior
OS to sorafenib (HR 0.86; 95.67% CI 0.73-1.03; non-inferiority
margin 1.08) with a median OS of 16.6 months versus 13.8, and an
improved tolerability profile versus sorafenib.
Summary of efficacy
resultsi:
|
STRIDE regimen
(n=393)
|
Imfinzi monotherapy
(n=389)
|
Sorafenib
(n=389)
|
OSii,iii
|
|
|
|
Number of patients with event (%)
|
262 (67)
|
280 (72)
|
293 (75)
|
Median OS (95% CI) (in months)
|
16.4
|
16.6
|
13.8
|
Hazard ratio (96.02% CI)
p-value
|
0.78 (0.65, 0.93)
0.0035
|
OS rate at 24 months (%)
|
40.5
|
39.6
|
32.6
|
OS rate at 36 months (%)
|
30.7
|
24.7
|
20.2
|
ORR (%)
|
20.1
|
17.0
|
5.1
|
Median DoR (months)
|
22.3
|
16.8
|
18.4
|
i. Analysis
was done at 71% maturity
ii. Investigator-assessed
OS data cut-off date was 27 August 2021
iii. Median (range)
follow-up durations at data cut-off: 33.18 (31.74-34.53), 32.56
(31.57-33.71) and 32.23 (30.42-33.71) months for STRIDE
regimen, Imfinzi monotherapy and sorafenib,
respectively.
The safety profiles of the STRIDE regimen and
for Imfinzi alone were consistent with the known
profiles of each medicine, and no new safety signals were
identified. Grade 3 or 4 treatment-related adverse events (AEs)
were experienced by 25.8% of patients treated with the STRIDE
regimen and by 12.9% of patients treated
with Imfinzi alone, versus 36.9% of patients on
sorafenib.
Incidence of Grade 3 or 4 treatment-related hepatic events were low
across treatment arms (5.9% for the STRIDE regimen and 5.2%
for Imfinzi, versus 4.5% for sorafenib). Treatment-related
AEs led to treatment discontinuation in 8.2% of patients treated
with the STRIDE regimen and 4.1% of patients treated
with Imfinzi alone, versus 11% for
sorafenib.
An additional presentation featured during the
ASCO Gastrointestinal Cancers Symposium will
showcase Imfinzi data from the TOPAZ-1 Phase III
trial, demonstrating the potential of this medicine in the
treatment of advanced biliary tract
cancer.
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.5 Chronic
liver diseases are associated with inflammation that over time can
lead to the development of HCC.5,6
More than half of HCC patients are diagnosed at advanced stages of
the disease, often when symptoms first appear.7 A
critical unmet need exists for patients with HCC who face limited
treatment options.7 The
unique immune environment of liver cancer provides clear rationale
for investigating medications that harness the power of the immune
system to treat HCC.7
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.
The trial included 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.
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, small cell lung cancer (SCLC), bladder cancer, several
gastrointestinal (GI) cancers, 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 GI cancers
AstraZeneca has a broad development programme for the treatment of
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.8
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,
biliary tract, 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. 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 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
January 2022.
2. WHO. Liver Cancer Fact Sheet. Available at:
https://gco.iarc.fr/today/data/factsheets/cancers/11-Liver-fact-sheet.pdf.
Accessed January 2022.
3. AstraZeneca data on file. Kantar Health. 2021.
4. Sayiner M, et al. Disease Burden of Hepatocellular Carcinoma:
A Global Perspective. Digestive Diseases and
Sciences. 2019; 64:
910-917.
5. 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.
6. Yu LX, et al. Role of nonresolving inflammation in
hepatocellular carcinoma development and
progression. Precision
Oncology. 2018:
2(8).
7. Colagrande S, et al. Challenges of advanced hepatocellular
carcinoma. World J
Gastroenterol. 2016;
22(34): 7645-7659.
8. WHO. World Cancer Fact Sheet. Available at:
https://gco.iarc.fr/today/data/factsheets/populations/900-world-fact-sheets.pdf.
Accessed January 2022.
Dr. Abou-Alfa has provided consulting services to
AstraZeneca.
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:
19 January 2022
|
By: /s/
Adrian Kemp
|
|
Name:
Adrian Kemp
|
|
Title:
Company Secretary
|