REG - AstraZeneca PLC - Tremelimumab US Priority Review for Imfinzi combo

AstraZenecaAnnouncement

25/04/2022 07:00

For best results when printing this announcement, please click on link below:
http://newsfile.refinitiv.com/getnewsfile/v1/story?guid=urn:newsml:reuters.com:20220425:nRSY1688Ja&default-theme=true

RNS Number : 1688J  AstraZeneca PLC  25 April 2022

25 April 2022 07:00 BST

 

Tremelimumab accepted under Priority Review in the US for patients

with unresectable liver cancer in combination with Imfinzi

 

STRIDE regimen of a single priming dose of tremelimumab added to Imfinzi is
the first dual immune checkpoint blockade regimen to improve overall survival
in a Phase III trial in this setting

 

AstraZeneca's Biologics License Application (BLA) for tremelimumab has been
accepted for Priority Review in the US, supporting the indication of a single
priming dose of the anti-CTLA4 antibody added to Imfinzi (durvalumab) for the
treatment of patients with unresectable hepatocellular carcinoma (HCC). A
supplemental BLA (sBLA) has also been submitted for Imfinzi in this
indication. This novel dose and schedule of the combination is called the
STRIDE regimen (Single Tremelimumab Regular Interval Durvalumab).

 

The Prescription Drug User Fee Act date, the Food and Drug Administration
(FDA) action date for their regulatory decision, is during the fourth quarter
of 2022 following the use of a priority review voucher.

 

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 26,000 people in the US present with advanced, unresectable HCC
each year.(3)

 

Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca,
said: "The HIMALAYA Phase III trial showed an unprecedented three-year overall
survival in this setting with a single priming dose of tremelimumab added to
Imfinzi, highlighting the potential for this regimen to improve longer-term
survival outcomes. Patients with advanced liver cancer are in great need of
new treatment options, and we are working closely with the FDA to bring this
novel approach to patients in the US as soon as possible."

 

The BLA for tremelimumab and sBLA for Imfinzi are based on final results
(https://www.astrazeneca.com/content/astraz/media-centre/press-releases/2022/imfinzi-plus-tremelimumab-unprecedented-survival-1st-line-unresectable-liver-cancer.html)
from the HIMALAYA Phase III trial presented at the 2022 American Society of
Clinical Oncology Gastrointestinal Cancers Symposium.

 

In this trial, 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).(4) Nearly one
in three (31%) patients were still alive at three years versus one in five
(20%) for sorafenib.(4)

 

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.

 

Imfinzi and tremelimumab were granted Orphan Drug Designation in the US for
the treatment of HCC in January 2020
(https://www.astrazeneca.com/media-centre/press-releases/2020/imfinzi-and-tremelimumab-granted-orphan-drug-designation-in-the-us-for-liver-cancer-20012020.html)
.

 

As part of its extensive clinical development programme in gastrointestinal
(GI) cancers, AstraZeneca is further assessing Imfinzi across multiple liver
cancer settings, including locoregional HCC (EMERALD-1, EMERALD-3) and
adjuvant HCC (EMERALD-2).

 

Notes

 

Liver Cancer

About 75% of all primary liver cancers are HCC.(1) Between 80-90% of all
patients with HCC also have cirrhosis.(5) Chronic liver diseases are
associated with inflammation that over time can lead to the development of
HCC.(5)

 

More than half of patients are diagnosed at advanced stages of the disease,
often when symptoms first appear.(6) A critical unmet need exists for patients
with HCC who face limited treatment options.(6) The unique immune environment
of liver cancer provides clear rationale for investigating medications that
harness the power of the immune system to treat HCC.(6)

 

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 181 centres across 16 countries, including in the
US, Canada, Europe, South America and Asia. The primary endpoint is overall
survival (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 tumourÕs 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 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.

 

In the past year, Imfinzi has demonstrated clinical benefit in multiple
additional cancer settings with positive Phase III trials in advanced biliary
tract cancer (TOPAZ-1), unresectable advanced liver cancer (HIMALAYA) and
metastatic NSCLC (POSEIDON).

 

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 small cell lung cancer, NSCLC, bladder cancer, several gastrointestinal
cancers, 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.

 

Beyond HIMALAYA, tremelimumab is being tested in combination
with Imfinzi across multiple tumour types including locoregional HCC
(EMERALD-3), SCLC (ADRIATIC) and bladder cancer (VOLGA and NILE).

 

Tremelimumab is also under review by global regulatory authorities in
combination with Imfinzi and chemotherapy in 1st-line metastatic NSCLC based
on the results of the POSEIDON Phase III trial, which showed the addition of a
short course of tremelimumab to Imfinzi plus chemotherapy improved both
overall and progression-free survival compared to chemotherapy alone.

 

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.(7)

 

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. In January 2022, results of the TOPAZ-1 Phase III trial
(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)
in 1st-line advanced biliary tract cancer demonstrated a significant
improvement in OS with Imfinzi plus standard-of-care chemotherapy versus
chemotherapy alone.

 

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 evasion of
the anti-tumour immune response. 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 targeted small 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
(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. Accessed
March 2022.

2.   WHO. Liver Cancer Fact Sheet. Available at:
https://gco.iarc.fr/today/data/factsheets/cancers/11-Liver-fact-sheet.pdf.
Accessed March 2022.

3.   AstraZeneca data on file. Kantar Health. 2021.

4.   Abou-Alfa GK, et al. Phase 3 randomized, open-label, multicenter study
of tremelimumab and durvalumab as first-line therapy in patients with
unresectable hepatocellular carcinoma: HIMALAYA. Presented at ASCO
Gastrointestinal Cancers Symposium 2022.

5.   Tarao K, et al. Real impact of liver cirrhosis on the development
of hepatocellular carcinoma in various liver diseasesÑmeta‐analytic
assessment. Cancer Med. 2019;8(3):1054-1065.  

6.   Colagrande S, et al. Challenges of advanced hepatocellular
carcinoma. World J Gastroenterol. 2016;22(34):7645-7659. 

7.   WHO. World Cancer Fact Sheet. Available at:
https://gco.iarc.fr/today/data/factsheets/cancers/39-All-cancers-fact-sheet.pdf.
Accessed March 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  MSCFIFFESEIEFIF