RNS Number : 2136P
15 October 2021
15 October 2021 7:00 BST
Imfinzi plus tremelimumab significantly improved overall
survival in HIMALAYA Phase III trial in 1st-line unresectable liver
Trial met primary endpoint of overall survival with a single
dose of tremelimumab plus Imfinzi every four weeks vs.
Imfinzi monotherapy met the overall survival endpoint of
non-inferiority vs. sorafenib
Positive high-level results from the HIMALAYA Phase III trial
showed a single, high priming dose of tremelimumab added to Imfinzi
(durvalumab) demonstrated a statistically significant and
clinically meaningful overall survival (OS) benefit versus
sorafenib as a 1st-line treatment for patients with unresectable
hepatocellular carcinoma (HCC) who had not received prior systemic
therapy and were not eligible for localised treatment . This novel
dose and schedule of tremelimumab, an anti-CTLA4 antibody, and
Imfinzi is called the STRIDE regimen (Single Tremelimumab Regular
Interval Durvalumab). The combination demonstrated a favourable
safety profile, and the addition of tremelimumab to Imfinzi did not
increase severe hepatic toxicity.
Imfinzi alone demonstrated non-inferior OS to sorafenib with a
numerical trend in favour of Imfinzi and an improved tolerability
profile compared to sorafenib.
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 with approximately 900,000 people diagnosed each
year.(1-2) Only 7% of patients with advanced disease survive five
Ghassan Abou-Alfa, MD, MBA, Attending Physician at Memorial
Sloan Kettering Cancer Center and principal investigator in the
HIMALAYA Phase III trial, said: " HIMALAYA is the first Phase III
trial to add a novel single priming dose of an anti-CTLA4 antibody
to another checkpoint inhibitor, durvalumab. This serves to boost
the patient's own immune system against their liver cancer, aiming
to maximise long-term survival with minimal side effects. This is
very exciting news for our patients."
Susan Galbraith, Executive Vice President, Oncology R&D,
AstraZeneca, said: "Inhibition of CTLA-4 has shown the ability to
drive benefit particularly in the tail of the survival curve in
several settings. This is the first time a dual immunotherapy
regimen has improved overall survival as a 1st-line treatment for
patients with unresectable liver cancer for whom treatment options
are limited and long-term outcomes are poor."
The data from the HIMALAYA Phase III trial will be presented at
a forthcoming medical meeting.
Imfinzi and tremelimumab were granted Orphan Drug Designations
in the US for the treatment of HCC in 2020. Tremelimumab was also
granted orphan designation in the EU in HCC in 2020.
About 75% of all primary liver cancers are HCC.(1) Between
80-90% of all patients with HCC also have cirrhosis, which is
primarily caused by infection with the hepatitis B or C viruses.(4)
Chronic liver diseases are associated with inflammation that, over
time, results in immunosuppression and can lead to the development
The unique immune environment of liver cancer provides clear
rationale for researching medicines that harness the power of the
immune system to treat HCC.(6) A critical unmet need exists for
patients with HCC who face limited treatment options.(6) More than
half of patients are diagnosed at advanced stages of the disease,
often when symptoms first appear.(6)
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, in 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
The trial was conducted in 190 centres across 16 countries,
including in the US, Canada, Europe, South America and Asia. The
primary endpoint was 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 (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.
I mfinzi 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 chemoradiation therapy 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.
Imfinzi is also approved for 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
In 1st-line Stage IV NSCLC, positive results from the POSEIDON
Phase III trial showed Imfinzi plus chemotherapy with a short
course of tremelimumab 75mg demonstrated a statistically
significant and clinically meaningful improvement in OS and PFS
compared to chemotherapy.
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 NSCLC, SCLC, bladder
cancer, HCC, biliary tract cancer (BTC), oesophageal cancer,
gastric and gastroesophageal cancer, cervical cancer, ovarian
cancer, endometrial cancer, and other solid tumours.
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.
Tremelimumab is being tested in a clinical trial programme in
combination with Imfinzi in NSCLC, SCLC, bladder cancer and liver
AstraZeneca in gastrointestinal cancers
AstraZeneca has a broad development programme for the treatment
of gastrointestinal (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, BTC, 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.(2) 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 anti-tumour immune suppression.
AstraZeneca is invested in using IO approaches that deliver
long-term survival for new groups of patients across tumour
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, small, targeted 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 (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 .
For details on how to contact the Investor Relations Team,
please click here . For Media contacts, click here .
1. ASCO. Liver Cancer: View All Pages. Available at:
Accessed October 2021.
2. WHO. Liver Cancer Fact Sheet. Available at:
. Accessed October 2021.
3. Sayiner M, et al. Disease Burden of Hepatocellular Carcinoma:
A Global Perspective. Digestive Diseases and Sciences. 2019; 64:
4. 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):
5. Yu LX, et al. Role of nonresolving inflammation in
hepatocellular carcinoma development and progression. Precision
Oncology. 2018: 2(8).
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:
. Accessed October 2021.
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 email@example.com or visit 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
(END) Dow Jones Newswires
October 15, 2021 02:00 ET (06:00 GMT)
Grafico Azioni Astrazeneca (LSE:AZN)
Da Ott 2021 a Nov 2021
Grafico Azioni Astrazeneca (LSE:AZN)
Da Nov 2020 a Nov 2021