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 December 2022
Commission File
Number: 001-11960
AstraZeneca
PLC
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AstraZeneca
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INDEX
TO EXHIBITS
1.
Imfinzi plus Imjudo recommended for approval in
the EU by CHMP for the treatment of advanced liver and lung
cancers
19
December 2022 07:10 GMT
Imfinzi plus Imjudo recommended
for approval in the EU
by CHMP for the treatment of advanced liver and lung
cancers
Positive opinions based on significant survival
benefit
in HIMALAYA and POSEIDON Phase III trials
AstraZeneca's Imfinzi (durvalumab) and Imjudo (tremelimumab) combinations have been
recommended for marketing authorisation in the European Union (EU)
for advanced liver and lung cancers.
The concurrent positive opinions recommend
authorising Imfinzi in combination with Imjudo for 1st-line treatment of adult patients
with advanced or unresectable hepatocellular carcinoma (HCC);
and Imfinzi in combination with Imjudo and platinum-based chemotherapy for the
treatment of adult patients with Stage IV (metastatic) non-small
cell lung cancer (NSCLC).
The Committee for Medicinal Products for Human Use
(CHMP) of the European Medicines Agency (EMA) based its
positive opinions on results from the HIMALAYA Phase
III trial, which was published in the New
England Journal of Medicine Evidence, and results from the POSEIDON Phase
III trial, which was published in the Journal
of Clinical Oncology.
Bruno Sangro, MD, PhD, Director of the Liver Unit
at Clínica Universidad de Navarra, Professor of Internal
Medicine at the University of Navarra School of Medicine and a lead
investigator in the HIMALAYA trial, said: "Liver cancer is a
leading cause of cancer death in Europe, and patients with advanced
disease face an especially grim prognosis with limited treatment
options in the 1st-line setting. The combination
of Imjudo and Imfinzi demonstrated a meaningful improvement in
overall survival with no increase in severe liver toxicity or
bleeding risk, which are important considerations for these
patients who often have advanced disease."
Solange Peters, MD, PhD, President of the European
Society for Medical Oncology (ESMO), head of the medical oncology
service and chair of thoracic oncology at Hospitalier Universitaire
Vaudois, Lausanne, Switzerland, and principal investigator in the
POSEIDON trial, said: "Metastatic non-small cell lung cancer
remains a complex and devastating diagnosis and there is still an
urgent need for new life-extending treatment options. The latest
data from the POSEIDON trial demonstrate the long-term survival
benefit of Imjudo added to Imfinzi and chemotherapy and support the important
role this novel combination could have for patients with metastatic
non-small cell lung cancer in Europe."
Susan Galbraith, Executive Vice President,
Oncology R&D, AstraZeneca, said: "Patients in Europe diagnosed
with these advanced cancers urgently need treatment combinations
that can help them live longer. If approved,
these Imjudo and Imfinzi combinations will provide patients with
novel options that harness the potential long-term survival
benefits seen with CTLA-4 inhibition."
Imjudo and Imfinzi in
liver cancer
The CHMP positive opinion for the treatment of HCC
is based on results from the HIMALAYA Phase III trial, in
which a single dose of the anti-CTLA-4
antibody Imjudo 300mg added to the anti-PD-L1
antibody Imfinzi 1500mg followed by Imfinzi every four weeks (STRIDE
regimen) reduced the risk of death by 22% versus sorafenib
(hazard ratio [HR] 0.78; 95% confidence interval [CI], 0.66-0.92;
p= 0.0035). An estimated 31% of patients treated with the
combination were still alive after three years, with 20% of
patients treated with sorafenib still alive at the same duration of
follow-up.
The safety profiles of the combination
of Imjudo added to Imfinzi and for Imfinzi alone were consistent with the known
profiles of each medicine, and no new safety signals were
identified.
Liver cancer is the third-leading cause of cancer
death and the sixth most commonly diagnosed cancer
worldwide.1,2 Approximately
87,000 Europeans were diagnosed with liver cancer in 2020, with 51%
of patients at an advanced cancer stage at time of diagnosis. Rates
of liver cancer continue to rise rapidly, with a 70% increase of
liver cancer-related mortality in the EU from
1990-2019.3
Imjudo and Imfinzi in
lung cancer
The CHMP positive opinion for the treatment
of metastatic NSCLC is based on results from the POSEIDON Phase III
trial, which showed patients treated with a limited course of five
cycles of the anti-CTLA-4 antibody Imjudo added to Imfinzi plus four cycles of platinum-based
chemotherapy experienced a 23% reduction in the risk of death
versus a range of chemotherapy options (HR 0.77; 95% CI, 0.65-0.92;
p=0.00304). An estimated 33% of patients were alive at two years
versus 22% for chemotherapy. This treatment combination also
reduced the risk of disease progression or death by 28% compared to
chemotherapy alone (HR 0.72; 95% CI, 0.60-0.86;
p=0.00031).
Updated
results from the POSEIDON
Phase III trial after approximately four years of follow-up
presented at the European Society for
Medical Oncology Congress 2022 demonstrated sustained survival benefit,
improving overall survival (OS) by 25% compared to chemotherapy
alone (HR 0.75; 95% CI, 0.63-0.88). An estimated 25% of patients
treated with the combination were alive at three years versus 13.6%
for those treated with chemotherapy alone.
The safety profile for Imjudo plus Imfinzi and chemotherapy was consistent with the
known profiles of each medicine, and no new safety signals were
identified.
Stage IV is the most advanced form of lung cancer
and is often referred to as metastatic disease.4,5 Approximately
40% of people with NSCLC have Stage IV disease at the time of
diagnosis.6 Almost
5% of patients with metastatic NSCLC in England will survive five
years after diagnosis, based on data between
2013-2017.7
In October 2022, Imjudo plus Imfinzi was approved in
the US for the treatment of adults with unresectable
HCC. Imjudo plus Imfinzi in combination with platinum-based
chemotherapy was approved in
the US in November 2022 for the treatment of adults with metastatic
NSCLC. Regulatory applications for both indications are also
currently under review in several other
countries based on the HIMALAYA and POSEIDON results,
respectively.
Notes
Liver cancer
About 75% of all
primary liver cancers in adults are HCC.1 Between
80-90% of all patients with HCC also have
cirrhosis.8 Chronic
liver diseases are associated with inflammation that over time can
lead to the development of HCC.8
More than half of patients are diagnosed at
advanced stages of the disease, often when symptoms first
appear.9 A
critical unmet need exists for patients with HCC who face limited
treatment options.9 The
unique immune environment of liver cancer provides clear rationale
for investigating medications that harness the power of the immune
system to treat HCC.9
Stage IV NSCLC
Lung cancer is the second most common form of
cancer globally, with more than two million patients diagnosed in
2020.10 Lung
cancer is broadly split into NSCLC and small-cell lung cancer
(SCLC), with 80-85% classified as NSCLC. Within NSCLC, patients are
classified as squamous, representing 25-30% of patients, or
non-squamous, representing approximately 70-75% of
patients.4,
11-12
HIMALAYA
HIMALAYA was a randomised, open-label,
multicentre, global Phase III trial of Imfinzi monotherapy
and a regimen comprising a single priming dose
of Imjudo 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 181 centres across 16
countries, including in the US, Canada, Europe, South America and
Asia. The primary endpoint was OS for the combination versus
sorafenib and key secondary endpoints included OS
for Imfinzi versus
sorafenib, objective response rate and progression-free survival
(PFS) for the combination and for Imfinzi alone.
POSEIDON
The POSEIDON trial was a randomised, open-label,
multi-centre, global, Phase III trial of Imfinzi plus platinum-based chemotherapy
or Imfinzi, tremelimumab and chemotherapy versus
chemotherapy alone in the 1st-line treatment of 1,013 patients with
metastatic NSCLC. The trial population included patients with
either non-squamous or squamous disease and the full range of PD-L1
expression levels. POSEIDON excluded patients with certain
epidermal growth factor receptor (EGFR) mutations or anaplastic
lymphoma kinase (ALK) fusions.
In the experimental arms, patients were treated
with a flat dose of either Imfinzi (1,500mg) or Imfinzi plus Imjudo (75mg) with up to four cycles of
chemotherapy every three weeks before
either Imfinzi maintenance once every four weeks or Imfinzi
and a fifth dose of Imjudo given at week 16. In comparison, the
control arm allowed up to six cycles of chemotherapy. Pemetrexed
maintenance treatment was allowed in all arms in patients with
non-squamous disease if given during the induction phase. Nearly
all patients with non-squamous disease (95.5%) had pemetrexed and
platinum, while the majority of patients with squamous disease
receiving chemotherapy (88.3%) received gemcitabine and
platinum.
Primary endpoints included PFS and OS for
the Imfinzi plus chemotherapy arm. Key secondary
endpoints included PFS and OS in the Imfinzi plus Imjudo and chemotherapy arm. As PFS endpoints were
met for both experimental arms, the prespecified statistical
analysis plan allowed for testing OS in
the Imfinzi plus Imjudo and
chemotherapy arm. The OS trend observed in
the Imfinzi plus chemotherapy arm did not achieve
statistical significance. The trial was conducted in more than 150
centres across 18 countries, including the US, Europe, South
America, Asia and South Africa.
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 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 SCLC based on the CASPIAN Phase III trial. In an
exploratory analysis 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 in combination
with Imjudo and chemotherapy in metastatic NSCLC in the
US; in combination with chemotherapy in locally advanced or
metastatic biliary tract cancer (BTC) in the US and several other
countries, in combination with Imjudo in unresectable HCC in the US and in
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 gastrointestinal (GI) cancers,
ovarian cancer, endometrial cancer and other solid
tumours.
Imjudo
Imjudo (tremelimumab) is a human monoclonal
antibody that targets the activity of cytotoxic
T-lymphocyte-associated protein 4
(CTLA-4). Imjudo blocks
the activity of CTLA-4, contributing to T-cell activation, priming
the immune response to cancer and fostering cancer cell
death.
In addition to its approved indications in liver
and lung cancers, Imjudo is being tested in combination
with Imfinzi across multiple tumour types including
locoregional HCC (EMERALD-3), SCLC (ADRIATIC) and bladder cancer
(VOLGA and NILE).
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.13
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,
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 lung cancer
AstraZeneca
is working to bring patients with lung cancer closer to cure
through the detection and treatment of early-stage disease, while
also pushing the boundaries of science to improve outcomes in the
resistant and advanced settings. By defining new therapeutic
targets and investigating innovative approaches, the Company aims
to match medicines to the patients who can benefit
most.
The Company's comprehensive portfolio includes
leading lung cancer medicines and the next wave of innovations,
including Tagrisso (osimertinib) and Iressa (gefitinib); Imfinzi (durvalumab) and Imjudo (tremelimumab); Enhertu (trastuzumab deruxtecan) and datopotamab
deruxtecan in collaboration with Daiichi
Sankyo; Orpathys (savolitinib) in collaboration with
HUTCHMED; as well as a pipeline of potential new medicines and
combinations across diverse mechanisms of
action.
AstraZeneca
is a founding member of the Lung Ambition Alliance, a global
coalition working to accelerate innovation and deliver meaningful
improvements for people with lung cancer, including and beyond
treatment.
AstraZeneca in immuno-oncology (IO)
AstraZeneca
is a pioneer in introducing the concept of immunotherapy into
dedicated clinical areas of high unmet medical need. The Company
has a comprehensive and diverse IO portfolio and pipeline anchored
in immunotherapies designed to overcome evasion of the anti-tumour
immune response and stimulate the body's immune system to attack
tumours.
AstraZeneca aims to reimagine cancer care and help
transform outcomes for patients with Imfinzi as a single treatment and in combination
with Imjudo as well as other novel immunotherapies and
modalities. The Company is also exploring next-generation
immunotherapies like bispecific antibodies and therapeutics that
harness different aspects of immunity to target
cancer.
AstraZeneca
is boldly pursuing an innovative clinical strategy to bring
IO-based therapies that deliver long-term survival to new settings
across a wide range of cancer types. With an extensive clinical
programme, the Company also champions the use of IO treatment in
earlier disease stages, where there is the greatest potential for
cure.
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 November 2022.
2. WHO. Liver Cancer
Fact Sheet. Available at: https://gco.iarc.fr/today/data/factsheets/cancers/11-Liver-fact-sheet.pdf.
Accessed November 2022.
3. EASL. Liver Cancer
Care Collaborative Projects. Available at: https://easl.eu/liver-cancer-care-collaborative-projects/.
Accessed November 2022.
4. Cancer.net.
Lung Cancer - Non-Small Cell: Stages. Available
at: https://www.cancer.net/cancer-types/lung-cancer-non-small-cell/stages.
Accessed November 2022.
5. American
Cancer Society. Non-Small
Cell Lung Cancer Stages. Available at: https://www.cancer.org/cancer/lung-cancer/detection-diagnosis-staging/staging-nsclc.html.
Accessed November 2022.
6. Engel-Nitz
N, et
al. Real-World
Costs of Adverse Events in First-Line Treatment of Metastatic
Non-Small Cell Lung Cancer. JMCP.
2020;26(6):729.
7. Cancer Research
UK. Lung cancer survival. Available at: https://www.cancerresearchuk.org/about-cancer/lung-cancer/survival. Accessed
November 2022.
8. 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.
9. Colagrande S, et
al. Challenges of advanced hepatocellular
carcinoma. World J
Gastroenterol. 2016;22(34):7645-7659.
10. WHO.
International Agency of Cancer Research. Lung Fact Sheet. Available
at: https://gco.iarc.fr/today/data/factsheets/cancers/15-Lung-fact-sheet.pdf. Accessed
November 2022.
11. Abernethy AP, et al. Real-world first-line treatment and overall
survival in non-small cell lung cancer without known EGFR mutations
or ALK rearrangements in US community oncology
setting. PLoS ONE. 2017;12(6):e0178420.
12. Cheema PK, et al. Perspectives on treatment advances for stage III
locally advanced unresectable non-small-cell lung
cancer. Curr Oncol. 2019;26(1):37-42.
13. WHO. World Cancer Fact
Sheet. Available
at: https://gco.iarc.fr/today/data/factsheets/populations/900-world-fact-sheets.pdf. Accessed
November 2022.
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 December 2022
|
|
By: /s/
Adrian Kemp
|
|
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Name:
Adrian Kemp
|
|
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Title:
Company Secretary
|
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