TIDMAZN
RNS Number : 8833Y
AstraZeneca PLC
19 January 2022
19 January 2022 07:00 GMT
Imfinzi plus tremelimumab demonstrated unprecedented survival in
1st-line unresectable liver cancer with 31% of patients alive at
three years
A single priming dose of tremelimumab plus Imfinzi every
four
weeks reduced risk of death by 22% in HIMALAYA Phase III
trial
Combination also showed no increase in severe liver toxicity and
fewer
discontinuations due to treatment-related adverse events vs.
sorafenib
Positive results from the HIMALAYA Phase III trial showed a
single priming dose of tremelimumab added to Imfinzi (durvalumab)
demonstrated a statistically significant and clinically meaningful
improvement in overall survival (OS) 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 Imfinzi and tremelimumab, an
anti-CTLA4 antibody, is called the STRIDE regimen (Single
Tremelimumab Regular Interval Durvalumab). Results from the trial
will be presented on 21 January at the 2022 American Society of
Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium.
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 80,000 people in the
US, Europe and Japan and 260,000 people in China present with
advanced, unresectable HCC each year.(3) Only 7% of patients with
advanced disease survive five years.(4)
Ghassan Abou-Alfa, MD, MBA, Attending Physician at Memorial
Sloan Kettering Cancer Center and principal investigator in the
HIMALAYA Phase III trial, said: "Patients with unresectable liver
cancer face a dismal prognosis, and new treatment options are
critical to improving long-term survival. The three-year overall
survival rate and favourable safety profile seen with the STRIDE
regimen set a new benchmark in this setting and underscore the
potential of this innovative treatment approach."
Susan Galbraith, Executive Vice President, Oncology R&D,
AstraZeneca, said: "The HIMALAYA trial reinforces our scientific
approach for tremelimumab, tapping into the potential of CTLA-4
inhibition and a unique dosing regimen to prime the immune system
to help patients live longer and with minimal side effects. We look
forward to bringing potential new treatment options to patients
with unresectable liver cancer, an area of high unmet need, as
quickly as possible."
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). Median OS was 16.4 months versus 13.8 for sorafenib. An
estimated 31% of patients were still alive at three years versus
20% for sorafenib.
Results also showed an increase in objective response rate (ORR)
with the STRIDE regimen versus sorafenib (20.1% vs. 5.1%). Median
duration of response (DoR) was 22.3 months with the STRIDE regimen
versus 18.4 with sorafenib. The addition of tremelimumab to Imfinzi
did not increase severe liver toxicity, and no bleeding risk was
observed.
HIMALAYA also tested Imfinzi monotherapy, which demonstrated
non-inferior OS to sorafenib (HR 0.86; 95.67% CI 0.73-1.03;
non-inferiority margin 1.08) with a median OS of 16.6 months versus
13.8, and an improved tolerability profile versus sorafenib.
Summary of efficacy results(i) :
STRIDE regimen Imfinzi monotherapy Sorafenib
(n=393) (n=389) (n=389)
OS(ii,iii)
--------------- -------------------- ----------
Number of patients
with event (%) 262 (67) 280 (72) 293 (75)
--------------- -------------------- ----------
Median OS (95% CI)
(in months) 16.4 16.6 13.8
--------------- -------------------- ----------
Hazard ratio (96.02% 0.78 (0.65, 0.93)
CI)
p-value 0.0035
-------------------------------------------------
OS rate at 24 months
(%) 40.5 39.6 32.6
--------------- -------------------- ----------
OS rate at 36 months
(%) 30.7 24.7 20.2
--------------- -------------------- ----------
ORR (%) 20.1 17.0 5.1
--------------- -------------------- ----------
Median DoR (months) 22.3 16.8 18.4
--------------- -------------------- ----------
i. Analysis was done at 71% maturity
ii. Investigator-assessed OS data cut-off date was 27 August 2021
iii. Median (range) follow-up durations at data cut-off: 33.18
(31.74-34.53), 32.56 (31.57-33.71) and 32.23 (30.42-33.71) months
for STRIDE regimen, Imfinzi monotherapy and sorafenib,
respectively.
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. Grade 3 or 4 treatment-related
adverse events (AEs) were experienced by 25.8% of patients treated
with the STRIDE regimen and by 12.9% of patients treated with
Imfinzi alone, versus 36.9% of patients on sorafenib.
Incidence of Grade 3 or 4 treatment-related hepatic events were
low across treatment arms (5.9% for the STRIDE regimen and 5.2% for
Imfinzi, versus 4.5% for sorafenib). Treatment-related AEs led to
treatment discontinuation in 8.2% of patients treated with the
STRIDE regimen and 4.1% of patients treated with Imfinzi alone,
versus 11% for sorafenib.
An additional presentation featured during the ASCO
Gastrointestinal Cancers Symposium will showcase Imfinzi data from
the TOPAZ-1 Phase III trial, demonstrating the potential of this
medicine in the treatment of advanced biliary tract cancer .
Notes
Liver cancer
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.(5)
Chronic liver diseases are associated with inflammation that over
time can lead to the development of HCC.(5,6)
More than half of HCC patients are diagnosed at advanced stages
of the disease, often when symptoms first appear.(7) A critical
unmet need exists for patients with HCC who face limited treatment
options.(7) The unique immune environment of liver cancer provides
clear rationale for investigating medications that harness the
power of the immune system to treat HCC.(7)
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 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
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 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 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 NSCLC, small cell lung
cancer (SCLC), bladder cancer, several gastrointestinal (GI)
cancers, cervical cancer, 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.
Tremelimumab is being tested in a clinical trial programme in
combination with Imfinzi in NSCLC, SCLC, bladder cancer and liver
cancer.
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.(8)
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.
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 anti-tumour immune suppression.
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 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
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 . ASCO. Liver Cancer: View All Pages. Available at:
https://www.cancer.net/cancer-types/liver-cancer/view-all. Accessed
January 2022.
2. WHO. Liver Cancer Fact Sheet. Available at:
https://gco.iarc.fr/today/data/factsheets/cancers/11-Liver-fact-sheet.pdf.
Accessed January 2022.
3. AstraZeneca data on file. Kantar Health. 2021.
4. Sayiner M, et al. Disease Burden of Hepatocellular Carcinoma:
A Global Perspective. Digestive Diseases and Sciences. 2019; 64:
910-917.
5. 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.
6. Yu LX, et al. Role of nonresolving inflammation in
hepatocellular carcinoma development and progression. Precision
Oncology. 2018: 2(8).
7. Colagrande S, et al. Challenges of advanced hepatocellular
carcinoma. World J Gastroenterol. 2016; 22(34): 7645-7659.
8. WHO. World Cancer Fact Sheet. Available at:
https://gco.iarc.fr/today/data/factsheets/populations/900-world-fact-sheets.pdf.
Accessed January 2022.
Dr. Abou-Alfa has provided consulting services to
AstraZeneca.
Adrian Kemp
Company Secretary
AstraZeneca PLC
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