REG - AstraZeneca PLC - Imfinzi + tremelimumab showed survival in POSEIDON

AstraZenecaAnnouncement

07/05/2021 07:00

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RNS Number : 8573X  AstraZeneca PLC  07 May 2021

7 May 2021 07:00 BST

 

Imfinzi and tremelimumab with chemotherapy demonstrated overall survival
benefit in POSEIDON trial for 1st-line Stage IV non-small cell lung cancer

 

First Phase III trial to demonstrate overall survival benefit with
tremelimumab

 

Imfinzi plus chemotherapy demonstrated progression-free survival benefit,

but a trend in overall survival did not achieve statistical significance

 

POSEIDON was a Phase III trial of AstraZeneca's Imfinzi (durvalumab) plus
platinum-based chemotherapy or Imfinzi, tremelimumab and chemotherapy versus
chemotherapy alone in the 1st-line treatment of patients with Stage IV
(metastatic) non-small cell lung cancer (NSCLC).

 

Positive high-level results from the final analysis of POSEIDON showed the
combination of Imfinzi, tremelimumab and chemotherapy demonstrated a
statistically significant and clinically meaningful overall survival (OS)
benefit versus chemotherapy alone. This immunotherapy combination also
demonstrated a statistically significant improvement in progression-free
survival (PFS) versus chemotherapy alone, as previously reported in October
2019
(https://www.astrazeneca.com/content/astraz/media-centre/press-releases/2019/imfinzi-and-imfinzi-plus-tremelimumab-delayed-disease-progression-in-phase-iii-poseidon-trial-for-1st-line-treatment-of-stage-iv-non-small-cell-lung-cancer.html)
. Patients in this arm were treated with a short course of tremelimumab, an
anti-CTLA4 antibody, over a 16-week period in addition to Imfinzi and standard
chemotherapy.

 

The Imfinzi plus chemotherapy arm demonstrated a statistically significant
improvement in PFS versus chemotherapy in the previous analysis, but the OS
trend observed in this analysis did not achieve statistical significance.
Patients in the control arm were treated with up to six cycles of
chemotherapy, while those in the experimental arms were treated with up to
four cycles.

 

Each combination demonstrated an acceptable safety profile, and no new safety
signals were identified. The combination with tremelimumab delivered a broadly
similar safety profile to the Imfinzi and chemotherapy combination and did not
lead to an increased discontinuation of treatment.

 

Dave Fredrickson, Executive Vice President, Oncology Business Unit, said: "We
are pleased to see the POSEIDON Phase III trial demonstrate, for the first
time, a significant and clinically meaningful overall survival benefit for
Imfinzi plus tremelimumab with chemotherapy in metastatic non-small cell lung
cancer. We were particularly pleased by the safety profile. We've seen
encouraging uptake of novel combinations in this setting and believe this new
approach will add a further option for patients with high unmet medical need.
We look forward to discussing next steps with regulatory authorities."

 

The data will be presented at a forthcoming medical meeting.

 

Imfinzi is the only approved immunotherapy in the curative-intent setting of
unresectable, Stage III NSCLC after chemoradiation therapy and is the global
standard of care based on the PACIFIC Phase III trial. Imfinzi is also
approved in the US, the EU, Japan and many 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 being further assessed across all stages of lung cancer as part of
an extensive Immuno-Oncology programme across NSCLC and SCLC, as well as in
other tumour types.

 

The combination of Imfinzi and tremelimumab is being tested in lung cancer,
bladder cancer and liver cancer settings.

 

Stage IV NSCLC

Lung cancer is the leading cause of cancer death accounting for about
one-fifth of all cancer deaths.(1) Patients are commonly diagnosed at Stage
IV, when the tumour has spread outside of the lung.(2)

 

Lung cancer is broadly split into NSCLC and SCLC, with 80-85% classified as
NSCLC.(2,3) Within NSCLC, patients are classified as squamous, representing
25-30% of patients, or non-squamous, the most common type representing
approximately 70-75% of NSCLC patients.(2) Stage IV is the most advanced form
of lung cancer and is often referred to as metastatic disease.(4)

 

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 1,500mg
of Imfinzi with up to four cycles of chemotherapy once every three weeks
or Imfinzi and 75mg of tremelimumab with chemotherapy, followed by
maintenance treatment with Imfinzi, or Imfinzi and one dose of
tremelimumab on a once-every-four-weeks dosing schedule. 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.

 

Primary endpoints included PFS and OS for the Imfinzi plus chemotherapy arm.
Key secondary endpoints included PFS and OS in the Imfinzi plus tremelimumab
and chemotherapy arm. As both PFS endpoints were met for Imfinzi plus
chemotherapy and Imfinzi, tremelimumab and chemotherapy, the prespecified
statistical analysis plan allowed for independent OS testing for the Imfinzi
plus tremelimumab and chemotherapy arm. 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 PD-L1 and
blocks the interaction of PD-L1 with PD-1 and CD80, countering the tumour's
immune-evading tactics and releasing the inhibition of immune responses.

 

In addition to approvals in the curative-intent setting of unresectable, Stage
III NSCLC and ES-SCLC, Imfinzi is approved for previously treated patients
with advanced bladder cancer in several countries.

 

As part of a broad development programme, Imfinzi is being tested as a
single treatment and in combinations with other anti-cancer medicines for
patients with NSCLC, SCLC, bladder cancer, hepatocellular carcinoma, biliary
tract cancer (a form of liver cancer), oesophageal cancer, gastric and
gastroesophageal cancer, 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 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 approaches, the Company aims
to match medicines to the patients who can benefit most.

 

The Company's comprehensive portfolio includes leading lung cancer medicines
such as the EGFR-TKIs Tagrisso (osimertinib) and Iressa (gefitinib), and the
PD-L1 inhibitor Imfinzi (durvalumab); alongside the CTLA-4 inhibitor
tremelimumab and the next wave of innovations, including the HER2-directed
antibody drug conjugate (ADC) Enhertu (trastuzumab deruxtecan) and the
TROP2-directed ADC datopotamab deruxtecan; and a pipeline of new molecules 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 immunotherapy

Immunotherapy is a therapeutic approach designed to stimulate the body's
immune system to attack tumours. The Company's 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 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

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 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
(https://www.astrazeneca.com/investor-relations.html#Contacts) . For Media
contacts, click here (https://www.astrazeneca.com/media-centre/contacts.html)
.

 

References

1.   World Health Organization. International Agency for Research on Cancer.
Lung Fact Sheet. Available at:
http://gco.iarc.fr/today/data/factsheets/cancers/15-Lung-fact-sheet.pdf
(http://gco.iarc.fr/today/data/factsheets/cancers/15-Lung-fact-sheet.pdf) .
Accessed May 2021.

2.   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.

3.   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.

4.   Cancer.Net. Lung Cancer - Non-Small Cell: Stages. Available at:
https://www.cancer.net/cancer-types/lung-cancer-non-small-cell/stages
(https://www.cancer.net/cancer-types/lung-cancer-non-small-cell/stages) .
Accessed May 2021.

 

Adrian Kemp

Company Secretary

AstraZeneca PLC

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