REG - AstraZeneca PLC - Imfinzi, Imjudo approved in Japan for 3 cancers

AstraZenecaAnnouncement

28/12/2022 07:00

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RNS Number : 9725K  AstraZeneca PLC  28 December 2022

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
(https://evidence.nejm.org/doi/full/10.1056/EVIDoa2100070) and TOPAZ-1
(https://evidence.nejm.org/doi/full/10.1056/EVIDoa2200015) Phase III trials,
each published in the New England Journal of Medicine Evidence and the
POSEIDON (https://ascopubs.org/doi/full/10.1200/JCO.22.00975) 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
(https://www.astrazeneca.com/media-centre/press-releases/2022/imfinzi-plus-tremelimumab-unprecedented-survival-1st-line-unresectable-liver-cancer.html)
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
(https://www.astrazeneca.com/media-centre/press-releases/2021/imfinzi-improves-survival-in-nsclc-in-poseidon.html)
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
(https://www.astrazeneca.com/media-centre/press-releases/2022/imfinzi-plus-chemotherapy-reduced-risk-of-death-by-20-in-1st-line-advanced-biliary-tract-cancer.html)
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
(https://www.astrazeneca.com/media-centre/press-releases/2022/imfinzi-and-tremelimumab-with-chemotherapy-demonstrated-sustained-survival-benefit-in-metastatic-non-small-cell-lung-cancer.html)
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
(https://www.astrazeneca.com/media-centre/press-releases/2022/imfinzi-plus-chemotherapy-further-improved-overall-survival-benefit-in-advanced-biliary-tract-cancer-in-the-topaz-1-phase-iii-trial.html)
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 (http://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.   World Health Organization. Japan Fact Sheet. Available at:
https://gco.iarc.fr/today/data/factsheets/populations/392-japan-fact-sheets.pdf
(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
(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
(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&
(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
(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
(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
(https://gco.iarc.fr/today/data/factsheets/populations/900-world-fact-sheets.pdf)
. Accessed December 2022.

 

Adrian Kemp

Company Secretary

AstraZeneca PLC

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