FORM
6-K
SECURITIES AND
EXCHANGE COMMISSION
Washington, D.C.
20549
Report
of Foreign Issuer
Pursuant to Rule
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the
Securities Exchange Act of 1934
For the
month of December 2022
Commission File
Number: 001-11960
AstraZeneca
PLC
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United
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AstraZeneca
PLC
INDEX
TO EXHIBITS
1.
Imfinzi, Imjudo approved in Japan for 3 cancers
28
December 2022 07:00 GMT
Imfinzi plus Imjudo approved
in Japan for advanced liver and non-small cell lung cancers,
and Imfinzi approved
for unresectable biliary tract and liver
cancers
Approvals based on significant survival benefits in
HIMALAYA, POSEIDON and TOPAZ-1 Phase III trials
AstraZeneca's
immunotherapies Imfinzi (durvalumab) and Imjudo (tremelimumab) have been approved in Japan
for the treatment of three cancer types: advanced liver, biliary
tract and lung.
The approvals authorise Imfinzi in combination with Imjudo for the treatment of adult patients with
unresectable hepatocellular carcinoma (HCC) and for the treatment
of adult patients with unresectable, advanced or recurrent
non-small cell lung cancer (NSCLC) in combination with
chemotherapy. Imfinzi was also authorised for the treatment of
adult patients with unresectable HCC as monotherapy and for the
treatment of adult patients with curatively unresectable biliary
tract cancer (BTC) in combination with chemotherapy (gemcitabine
plus cisplatin).
The concurrent approvals by the Japanese Ministry
of Health, Labour, and Welfare are based on positive results from
the HIMALAYA and TOPAZ-1 Phase
III trials, each published in the New England Journal of
Medicine Evidence and
the POSEIDON Phase
III trial, published in the Journal of Clinical
Oncology.
Dave Fredrickson, Executive Vice President,
Oncology Business Unit, AstraZeneca, said: "Japan has one of the
highest rates of diagnosis for liver and biliary tract cancers in
the world, and lung cancer remains the country's leading cause of
cancer death. With these approvals for Imfinzi and Imjudo, patients in Japan can now be treated with novel
immunotherapy-based treatment regimens that have demonstrated
significant survival benefits across three complex cancers with
poor prognoses."
Imfinzi and Imjudo approved
in liver cancer
The approval of Imfinzi in combination with Imjudo for the treatment of unresectable HCC brings
the first dual immunotherapy treatment regimen to patients in
Japan. The approval 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: Single
Tremelimumab Regular Interval Durvalumab)
significantly reduced the risk of death versus sorafenib. The
addition of Imjudo to Imfinzi did not increase severe liver toxicity, and
no bleeding risk was observed.
HIMALAYA also served as the basis for the approval
of Imfinzi monotherapy in the same disease setting. In
HIMALAYA, Imfinzi demonstrated non-inferior overall survival
(OS) compared to sorafenib, and an improved tolerability profile
versus sorafenib.
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 fifth-leading cause of cancer
death in Japan and the sixth most commonly diagnosed cancer
worldwide.1,2 HCC
is the most common type of liver cancer with 80% of cases occurring
in the Asia-Pacific region.3,4 In
Japan, approximately 45,000 people are diagnosed with HCC and
32,000 die of the disease each year.5,6
Imfinzi and Imjudo approved
in NSCLC
The approval of Imfinzi and Imjudo plus chemotherapy for the treatment of
unresectable, advanced or recurrent NSCLC is based
on results from
the POSEIDON Phase III trial, which showed a limited course of
five cycles of the anti-CTLA-4 antibody Imjudo added to Imfinzi plus four cycles of platinum-based
chemotherapy significantly reduced the risk of death versus a range
of chemotherapy options.
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.
In Japan, lung cancer is the most commonly
diagnosed cancer, with more than 138,000 patients diagnosed in
2020.1 The
prognosis for patients with metastatic NSCLC in Japan is
particularly poor, as less than 20% will live beyond three years
after diagnosis without treatment.7
Regulatory applications
for Imfinzi and Imjudo are currently under review in the EU and
several other countries based on the HIMALAYA, TOPAZ-1 and POSEIDON
results.
Imfinzi plus
chemotherapy approved in biliary tract
cancer
The approval of Imfinzi plus chemotherapy brings the first
immunotherapy regimen to patients with curatively unresectable BTC
in Japan after more than a decade of limited innovation. The
approval is based on results from an interim
analysis of the TOPAZ-1
Phase III trial, which showed that Imfinzi plus chemotherapy significantly reduced the
risk of death compared to chemotherapy
alone. Imfinzi plus chemotherapy was generally well
tolerated and did not increase the discontinuation rate due to
adverse events compared to chemotherapy alone.
BTC is a group of rare and aggressive cancers that
occur in the bile ducts and gallbladder.8,9 In
2021, approximately 23,300 people in Japan were diagnosed with BTC,
which is the sixth-leading cause of cancer-related deaths for women
and seventh-leading cause of cancer-related death for men in
Japan.7 Patients
face a poor prognosis, with approximately 19% to 31% of patients
with BTC surviving five years.7
Notes
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 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
(ORR) and progression-free survival (PFS) for the combination and
for Imfinzi alone.
In HIMALAYA, the 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.
POSEIDON
The POSEIDON trial was a randomised, open-label,
multi-centre, global, Phase III trial of Imfinzi plus platinum-based chemotherapy,
or Imfinzi, Imjudo 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 both PFS endpoints
were met for Imfinzi plus chemotherapy
and Imfinzi, Imjudo and chemotherapy, the prespecified
statistical analysis plan allowed for testing OS in
the Imfinzi plus Imjudo and chemotherapy arm. The trial was
conducted in more than 150 centres across 18 countries, including
the US, Europe, South America, Asia and South
Africa.
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 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.
TOPAZ-1
TOPAZ-1 was 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 was OS and key secondary endpoints included PFS,
ORR 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.
At the interim analysis, Imfinzi plus chemotherapy 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;
p=0.021). Updated
results from TOPAZ-1 after
an additional 6.5 months of follow-up showed a 24% reduction in the
risk of death versus chemotherapy alone (HR 0.76; 95% CI,
0.64-0.91), with more than two times as many patients treated
with Imfinzi plus chemotherapy estimated to be alive at
two years versus chemotherapy alone (23.6% versus 11.5%). Updated
median overall survival (OS) was 12.9 months versus 11.3 with
chemotherapy. Imfinzi plus chemotherapy was generally well
tolerated, with no new safety signals observed, and did not
increase the discontinuation rate due to adverse events (AEs)
compared to chemotherapy 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 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 in combination
with Imjudo and chemotherapy in metastatic non-small
cell lung cancer in the US and Japan; in combination with
chemotherapy in locally advanced or metastatic BTC in the US, Japan
and several other countries; in combination
with Imjudo in unresectable HCC in the US and Japan; as
monotherapy in unresectable HCC in Japan; 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.10
Within
this programme, the Company is committed to improving outcomes in
gastric, liver, BTC, oesophageal, pancreatic, and colorectal
cancers.
Imfinzi is approved in the US and several other
countries in combination with chemotherapy (gemcitabine plus
cisplatin) for advanced biliary tract cancer and in the US and
Japan in combination with Imjudo in unresectable
HCC. Imfinzi is
also approved as a monotherapy in unresectable HCC in
Japan. Imfinzi is being assessed in combinations, including
with Imjudo, in liver, oesophageal and gastric cancers in
an extensive development programme spanning early to late-stage
disease across settings.
Enhertu (trastuzumab deruxtecan), a HER2-directed
antibody drug conjugate, is approved in the US and several other
countries for HER2-positive advanced gastric cancer and is being
assessed in colorectal cancer. Enhertu is jointly developed and commercialised by
AstraZeneca and Daiichi Sankyo.
Lynparza (olaparib), a first-in-class PARP inhibitor,
is approved in the US and several other countries for the treatment
of BRCA-mutated metastatic pancreatic
cancer. 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 and Imjudo; Enhertu 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. World Health
Organization. Japan Fact Sheet. Available at: https://gco.iarc.fr/today/data/factsheets/populations/392-japan-fact-sheets.pdf.
Accessed December 2022.
2. World Health
Organization. Liver Cancer Fact Sheet. Available
at: https://gco.iarc.fr/today/data/factsheets/cancers/11-Liver-fact-sheet.pdf.
Accessed December 2022.
3. ASCO. Liver Cancer: View All
Pages. Available at: https://www.cancer.net/cancer-types/liver-cancer/view-all.
Accessed December 2022.
4. Boyle DA. Hepatocellular carcinoma:
Implications for Asia-Pacific Oncology
Nurses. Asia Pac J Oncol
Nurs.
2017;(4)2.98-103.
5. World Health
Organization. International Agency for Research on Cancer.
Estimated number of new cases in 2020, Japan, both sexes, all ages
(excl. NMSC). Available at: https://gco.iarc.fr/today/online-analysis-table?v=2020&mode=cancer&mode_population=continents&population=392&populations=392&key=asr&sex=0&cancer=39&type=0&statistic=5&prevalence=0&population_group=0&ages_group%5B%5D=0&ages_group%5B%5D=17&group_cancer=1&.
Accessed December 2022.
6. Ikeda M, et al. Current status of hepatocellular carcinoma in
Japan. Chin Clin
Oncol.
2013;2(4):40.
7. Foundation for
Promotion of Cancer Research. Cancer Statistics in Japan - 2022.
Available at: https://ganjoho.jp/public/qa_links/report/statistics/pdf/cancer_statistics_2022.pdf.
Accessed December 2022.
8. Marcano-Bonilla
L, et
al. Biliary tract cancers:
epidemiology, molecular pathogenesis and genetic risk
associations. CCO.
2016;5(5).
9. 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 December 2022.
10. World Health
Organization. World Cancer Fact Sheet. Available
at: https://gco.iarc.fr/today/data/factsheets/populations/900-world-fact-sheets.pdf.
Accessed December 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:
28 December 2022
|
|
By: /s/
Adrian Kemp
|
|
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Name:
Adrian Kemp
|
|
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Title:
Company Secretary
|
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