REG - AstraZeneca PLC - Imfinzi + Imjudo recommended for approvals in EU

AstraZenecaAnnouncement

19/12/2022 07:15

For best results when printing this announcement, please click on link below:
http://newsfile.refinitiv.com/getnewsfile/v1/story?guid=urn:newsml:reuters.com:20221219:nRSS0761Ka&default-theme=true

RNS Number : 0761K  AstraZeneca PLC  19 December 2022

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
(https://www.astrazeneca.com/media-centre/press-releases/2022/imfinzi-plus-tremelimumab-unprecedented-survival-1st-line-unresectable-liver-cancer.html)
Phase III trial, which was published in the New England Journal of Medicine
Evidence (https://evidence.nejm.org/doi/full/10.1056/EVIDoa2100070) , and
results from the POSEIDON
(https://www.astrazeneca.com/media-centre/press-releases/2021/imfinzi-improves-survival-in-nsclc-in-poseidon.html)
Phase III trial, which was published in the Journal of Clinical Oncology
(https://ascopubs.org/doi/10.1200/JCO.22.00975?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed)
.

 

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
(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)
from the POSEIDON Phase III trial 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.

 

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
(https://www.astrazeneca.com/media-centre/press-releases/2022/imfinzi-and-imjudo-approved-in-advanced-liver-cancer.html#!)
in the US for the treatment of adults with unresectable HCC. Imjudo plus
Imfinzi in combination with platinum-based chemotherapy was approved
(https://www.astrazeneca.com/media-centre/press-releases/2022/imfinzi-and-imjudo-approved-in-us-for-lung-cancer.html)
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
(https://www.astrazeneca.com/media-centre/press-releases/2021/imfinzi-improved-survival-in-biliary-tract-cancer.html)
 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.   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
November 2022.

2.   WHO. 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 November 2022.

3.   EASL. Liver Cancer Care Collaborative Projects. Available at:
https://easl.eu/liver-cancer-care-collaborative-projects/
(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
(https://www.cancer.net/cancer-types/lung-cancer-non-small-cell/stages.%20Accessed%20November%202022)
.

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
(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
(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
(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
(https://gco.iarc.fr/today/data/factsheets/populations/900-world-fact-sheets.pdf)
. Accessed November 2022.

 

Adrian Kemp

Company Secretary

AstraZeneca PLC

This information is provided by RNS, the news service of the London Stock Exchange. RNS is approved by the Financial Conduct Authority to act as a Primary Information Provider in the United Kingdom. Terms and conditions relating to the use and distribution of this information may apply. For further information, please contact
rns@lseg.com (mailto:rns@lseg.com)
 or visit
www.rns.com (http://www.rns.com/)
.

RNS may use your IP address to confirm compliance with the terms and conditions, to analyse how you engage with the information contained in this communication, and to share such analysis on an anonymised basis with others as part of our commercial services. For further information about how RNS and the London Stock Exchange use the personal data you provide us, please see our
Privacy Policy (https://www.lseg.com/privacy-and-cookie-policy)
.   END  MSCFFEFWAEESEDE