REG - AstraZeneca PLC - Imfinzi + Imjudo approved in advanced liver cancer

AstraZenecaAnnouncement

24/10/2022 07:00

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RNS Number : 8408D  AstraZeneca PLC  24 October 2022

24 October 2022 07:00 BST

 

Imjudo (tremelimumab) in combination with Imfinzi approved

in the US for patients with unresectable liver cancer

 

Approval based on HIMALAYA Phase III trial results which showed single priming
dose of Imjudo added to Imfinzi reduced risk of death by 22% vs. sorafenib

 

AstraZeneca's Imjudo (tremelimumab) in combination with Imfinzi (durvalumab)
has been approved in the US for the treatment of adult patients with
unresectable hepatocellular carcinoma (HCC), the most common type of liver
cancer. The novel dose and schedule of the combination, which includes 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, is called the
STRIDE regimen (Single Tremelimumab Regular Interval Durvalumab).

 

The approval by the US Food and Drug Administration (FDA) was based on
positive results from the HIMALAYA Phase III trial. In this trial, patients
treated with the combination of Imjudo and Imfinzi experienced a 22% reduction
in the risk of death versus sorafenib (based on a hazard ratio  HR  of 0.78,
95% confidence interval  CI  0.66-0.92 p=0.0035).(1) Results were also
published in the New England Journal of Medicine Evidence
(https://evidence.nejm.org/doi/full/10.1056/EVIDoa2100070) showing that 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.(2)

 

Liver cancer is the third-leading cause of cancer death and the sixth most
commonly diagnosed cancer worldwide.(3,4) It is the fastest rising cause of
cancer-related deaths in the US, with approximately 36,000 new diagnoses each
year.(5,6)

 

Ghassan Abou-Alfa, MD, MBA, Attending Physician at Memorial Sloan Kettering
Cancer Center (MSK), and principal investigator in the HIMALAYA Phase III
trial, said: "Patients with unresectable liver cancer are in need of
well-tolerated treatments that can meaningfully extend overall survival. In
addition to this regimen demonstrating a favourable three-year survival rate
in the HIMALAYA trial, safety data showed no increase in severe liver toxicity
or bleeding risk for the combination, important factors for patients with
liver cancer who also have advanced liver disease."

 

Dave Fredrickson, Executive Vice President, Oncology Business Unit,
AstraZeneca, said: "With this first regulatory approval for Imjudo, patients
with unresectable liver cancer in the US now have an approved dual
immunotherapy treatment regimen that harnesses the potential of CTLA-4
inhibition in a unique combination with a PD-L1 inhibitor to enhance the
immune response against their cancer."

Andrea Wilson Woods, President & Founder, Blue Faery: The Adrienne Wilson
Liver Cancer Foundation, said: "In the past, patients living with liver cancer
had few treatment options and faced poor prognoses. With today's approval, we
are grateful and optimistic for new, innovative, therapeutic options. These
new treatments can improve long-term survival for those living with
unresectable hepatocellular carcinoma, the most common form of liver cancer.
We appreciate the patients, their families, and the broader liver cancer
community who continue to fight for new treatments and advocate for others."

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.

Regulatory applications for Imjudo in combination with Imfinzi are currently
under review in Europe, Japan and several other countries for the treatment of
patients with advanced liver cancer based on the HIMALAYA results.

 

Notes

 

Liver cancer

About 75% of all primary liver cancers in adults are HCC.(3) Between 80-90%
of all patients with HCC also have cirrhosis.(7)( )Chronic liver diseases are
associated with inflammation that over time can lead to the development of
HCC.(7)

More than half of patients are diagnosed at advanced stages of the disease,
often when symptoms first appear.(8) A critical unmet need exists for
patients with HCC who face limited treatment options.(8) The unique immune
environment of liver cancer provides clear rationale for investigating
medications that harness the power of the immune system to treat HCC.(8)

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 overall
survival (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.

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 was recently approved to treat patients with advanced biliary tract
cancer in the US based on results from the TOPAZ-1 Phase III trial. It 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.

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 SCLC, NSCLC, bladder cancer, several gastrointestinal (GI)
cancers, ovarian cancer, endometrial cancer, and other solid tumours.

Imfinzi combinations have also demonstrated clinical benefit in metastatic
NSCLC in the POSEIDON Phase III trial.

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.

Beyond HIMALAYA, 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).

Imjudo 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 Imjudo 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.(9)

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 in 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 immuno-oncology (IO)

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 Imjudo
(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)
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Contacts
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References

1.   Imfinzi and Imjudo US prescribing information; 2022.

2.   Abou-Alfa, et al. Tremelimumab plus Durvalumab in Unresectable
Hepatocellular Carcinoma. NEJM Evid. 2022;1-12.

3.   ASCO. Liver Cancer: View All Pages. Available at:
https://www.cancer.net/cancer-types/liver-cancer/view-all. Accessed October
2022.

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

5.   Rawla, P, et al. Update in global trends and aetiology of
hepatocellular carcinoma. Contemp Oncol (Pozn). 2018; 22(3): 141-150.

6.   CDC. Liver Cancer. Available at:
https://www.cdc.gov/cancer/liver/index.htm
(https://www.cdc.gov/cancer/liver/index.htm) . Accessed: October 2022.

7.   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.  

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

9.   WHO. World Cancer Fact Sheet. Available at:
https://gco.iarc.fr/today/data/factsheets/cancers/39-All-cancers-fact-sheet.pdf.
Accessed October 2022.

 

Adrian Kemp

Company Secretary

AstraZeneca PLC

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