a0057i
FORM 6-K
SECURITIES
AND EXCHANGE COMMISSION
Washington,
D.C. 20549
Report
of Foreign Issuer
Pursuant
to Rule 13a-16 or 15d-16 of
the
Securities Exchange Act of 1934
For the
month of March
2020
Commission
File Number: 001-11960
AstraZeneca PLC
1
Francis Crick Avenue
Cambridge
Biomedical Campus
Cambridge
CB2 0AA
United
Kingdom
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AstraZeneca PLC
INDEX
TO EXHIBITS
1.
Imfinzi approved
in the US for extensive-stage small cell lung
cancer
30 March 2020 07:00 BST
Imfinzi approved
in the US for extensive-stage small cell lung
cancer
Only PD-1/PD-L1 immunotherapy to demonstrate a significant survival
benefit in combination with etoposide and a choice of carboplatin
or cisplatin chemotherapy
AstraZeneca's Imfinzi (durvalumab) has been approved in the US as
a 1st-line treatment for adult patients with extensive-stage small
cell lung cancer (ES-SCLC) in combination with standard-of-care
(SoC) chemotherapies, etoposide plus either carboplatin or
cisplatin (platinum-etoposide).
The approval by the Food and Drug Administration was
based on positive results from the Phase III CASPIAN
trial showing Imfinzi in combination with SoC platinum-etoposide
demonstrated a statistically significant and clinically meaningful
improvement in overall survival (OS) versus SoC
alone.
SCLC is a highly aggressive, fast-growing form of lung cancer that
typically recurs and progresses rapidly despite initial response to
chemotherapy.1,2
Dave Fredrickson, Executive Vice President, Oncology Business Unit,
said: "The US approval of Imfinzi brings a new medicine to extensive-stage
small cell lung cancer patients in urgent need of new
options. Imfinzi is the only immunotherapy to show both a
significant survival benefit and improved response rate in
combination with chemotherapy for these patients, an important step
forward in treating this devastating disease."
Jonathan Goldman, MD, Associate Professor of Hematology &
Oncology, UCLA Medical Center, Santa Monica, California and a lead
investigator in the Phase III CASPIAN trial, said: "Patients with
extensive-stage small cell lung cancer continue to face a poor
prognosis, and finding new medicines to improve outcomes in this
setting has been a formidable challenge. The CASPIAN trial enables
clinicians to choose durvalumab in combination with etoposide and
either carboplatin or cisplatin, making this an important new
1st-line treatment option for patients that is both effective and
well-tolerated."
The Phase III CASPIAN trial had two primary endpoints comparing
experimental arms to SoC. In the Imfinzi plus SoC arm, the risk of death was reduced
by 27% (equal to a hazard ratio of 0.73; 95% CI 0.59-0.91;
p=0.0047), with median OS of 13.0 months versus 10.3 months for SoC
alone. Results also showed an increased confirmed objective
response rate in the Imfinzi plus SoC arm (68% versus 58% for SoC
alone). The safety and tolerability
for Imfinzi plus SoC was consistent with the known
safety profiles of these
medicines. The Imfinzi plus SoC data from the CASPIAN trial were
published in The
Lancet.3
The second experimental arm testing tremelimumab added
to Imfinzi and SoC recently
completed, but did not meet its
primary endpoint. Details will be presented at a forthcoming
medical meeting.
The CASPIAN trial used a fixed dose of Imfinzi (1500mg) administered every three weeks for
four cycles while in combination with chemotherapy and then every
four weeks until disease progression. As part of a broad
development programme, Imfinzi is also being tested following
concurrent chemoradiation therapy in patients with limited-stage
SCLC in the Phase III ADRIATIC trial with data anticipated in
2021.
Imfinzi received its first
approval based on the Phase III CASPIAN trial in Singapore for
patients with ES-SCLC in February 2020. Imfinzi in combination with etoposide and either
carboplatin or cisplatin is currently under regulatory review for
the treatment of ES-SCLC in the 1st-line setting based on the Phase
III CASPIAN trial in the EU and Japan.
Small cell lung cancer
Lung
cancer is the leading cause of cancer death among both men and
women and accounts for about one fifth of all cancer
deaths.4 Lung
cancer is broadly split into non-small cell lung cancer (NSCLC) and
SCLC, with about 15% classified as SCLC.5 About
two thirds of SCLC patients are diagnosed with ES-SCLC, in which
the cancer has spread widely through the lung or to other parts of
the body.6 Prognosis
is particularly poor, as only 6% of all SCLC patients will be alive
five years after diagnosis.6
CASPIAN
CASPIAN was a randomised, open-label, multi-centre, global, Phase
III trial in the 1st-line treatment of 805 patients with ES-SCLC.
The trial compared Imfinzi in combination with etoposide and either
carboplatin or cisplatin chemotherapy, or Imfinzi and chemotherapy with the addition of a
second immunotherapy, tremelimumab, versus chemotherapy alone. In
the experimental arms, patients were treated with four cycles of
chemotherapy. In comparison, the control arm allowed up to six
cycles of chemotherapy and optional prophylactic cranial
irradiation. The trial was conducted in more than 200 centres
across 23 countries, including the US, in Europe, South America,
Asia and the Middle East. The primary endpoint was OS in each of
the two experimental arms.
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.
Imfinzi is approved in the
curative-intent setting of unresectable, Stage III NSCLC after
chemoradiation therapy in the US, Japan, China, across the EU and
in many other countries, based on the Phase III PACIFIC
trial. Imfinzi is approved for the 1st-line treatment of
ES-SCLC in combination with SoC chemotherapy in the US and
Singapore. Imfinzi is
also approved for previously treated patients with advanced bladder
cancer in the US and a small number of other
countries.
As part of a broad development programme, Imfinzi is also being tested as a monotherapy and in
combination with tremelimumab, an anti-CTLA4 monoclonal antibody
and potential new medicine, as a treatment for patients with NSCLC,
SCLC, bladder cancer, head and neck cancer, liver cancer, biliary
tract cancer, cervical 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, head and
neck cancer and liver cancer.
AstraZeneca in lung cancer
AstraZeneca has a comprehensive portfolio of approved and potential
new medicines in late-stage development for the treatment of
different forms of lung cancer spanning different histologies,
several stages of disease, lines of therapy and modes of action. We
aim to address the unmet needs of patients with EGFR-mutated
tumours as a genetic driver of disease, which occur in 10-15% of
NSCLC patients in the US and EU and 30-40% of NSCLC patients in
Asia, with the approved medicines Iressa (gefitinib) and Tagrisso (osimertinib), and its ongoing Phase III
trials ADAURA, LAURA, and FLAURA2.7-9 We
are also committed to addressing tumour mechanisms of resistance
through the ongoing Phase II trials SAVANNAH and ORCHARD which
test Tagrisso in combination with savolitinib, a selective
inhibitor of c-MET receptor tyrosine kinase, along with other
potential new medicines. Enhertu (trastuzumab deruxtecan), a HER2-directed
antibody drug conjugate is in development for metastatic
non-squamous HER2-overexpressing or HER2-mutated NSCLC including
trials in combination with other anticancer
treatments.
An extensive late-stage Immuno-Oncology programme focuses on lung
cancer patients without a targetable genetic mutation which
represents up to three-quarters of all patients with lung
cancer.10 Imfinzi,
an anti-PDL1 antibody, is in development for patients with advanced
disease (Phase III trials POSEIDON and PEARL) and for patients in
earlier stages of disease including potentially-curative settings
(Phase III trials AEGEAN, ADJUVANT BR.31, PACIFIC-2, PACIFIC-4,
PACIFIC-5, and ADRIATIC) both as monotherapy and in combination
with tremelimumab and/or chemotherapy. Imfinzi is also in development in the Phase II
combination trials NeoCOAST, COAST and HUDSON in combination with
potential new medicines from the early-stage
pipeline.
AstraZeneca's approach to Immuno-Oncology (IO)
Immuno-oncology (IO) is a therapeutic approach designed to
stimulate the body's immune system to attack tumours. The Company's
IO portfolio is anchored by immunotherapies that have been designed
to overcome anti-tumour immune suppression. AstraZeneca believes
that IO-based therapies offer the potential for life-changing
cancer treatments for the clear majority of patients.
The Company is pursuing a comprehensive clinical-trial programme
that includes Imfinzi as a monotherapy and in combination with
tremelimumab in multiple tumour types, stages of disease, and lines
of therapy, 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 has a deep-rooted heritage in oncology and offers a
quickly growing portfolio of new medicines that has the potential
to transform patients' lives and the Company's future. With six new
medicines launched between 2014 and 2020, and a broad pipeline of
small molecules and biologics in development, the Company is
committed to advance oncology as a key growth driver for
AstraZeneca focused on lung, ovarian, breast and blood cancers. In
addition to AstraZeneca's main capabilities, the Company is
actively pursuing innovative partnerships and investments that
accelerate the delivery of our strategy, as illustrated by the
investment in Acerta Pharma in haematology.
By harnessing the power of four scientific platforms -
Immuno-Oncology, Tumour Drivers and Resistance, DNA Damage Response
and Antibody Drug Conjugates - and by championing the development
of personalised combinations, AstraZeneca has the vision to
redefine cancer treatment and one day eliminate cancer as a cause
of death.
AstraZeneca
AstraZeneca (LSE/STO/NYSE: AZN) is a global, science-led
biopharmaceutical company that focuses on the discovery,
development and commercialisation of prescription medicines,
primarily for the treatment of diseases in three therapy areas -
Oncology, Cardiovascular, Renal and Metabolism, and Respiratory.
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. National Cancer
Institute. NCI Dictionary - Small Cell Lung Cancer. Available
at https://www.cancer.gov/publications/dictionaries/cancer-terms/def/small-cell-lung-cancer.
Accessed March 2020.
2. Kalemkerian
GP, et
al. Treatment Options for
Relapsed Small-Cell Lung Cancer: What Progress Have We
Made? Journal of Oncology
Practice, volume 14, issue no.
6 (June 1, 2018) 369-370.
3. Paz-Ares,
L. et
al. Durvalumab plus
platinum-etoposide versus platinum-etoposide in first-line
treatment of extensive-stage small-cell lung cancer (CASPIAN): a
randomised, controlled, open-label, phase 3
trial. The Lancet, 2019;394(10212):1929-1939.
4. World Health
Organization. International Agency for Research on Cancer.
Available at http://gco.iarc.fr/today/data/factsheets/cancers/15-Lung-fact-sheet.pdf.
Accessed March 2020.
5. LUNGevity
Foundation. Types of Lung Cancer. Available
at https://lungevity.org/for-patients-caregivers/lung-cancer-101/types-of-lung-cancer.
Accessed March 2020.
6. Cancer.Net. Lung
Cancer - Small Cell. Available at https://www.cancer.net/cancer-types/33776/view-all.
Accessed March 2020.
7. Szumera-Ciećkiewicz
A, et
al. EGFR Mutation Testing on
Cytological and Histological Samples in Non-Small Cell Lung Cancer:
a Polish, Single Institution Study and Systematic Review of
European Incidence. Int J Clin Exp
Pathol.
2013:6;2800-12.
8. Keedy VL, et al. American Society of Clinical Oncology
Provisional Clinical Opinion: Epidermal Growth Factor Receptor
(EGFR) Mutation Testing for Patients with Advanced Non-Small-Cell
Lung Cancer Considering First-Line EGFR Tyrosine Kinase Inhibitor
Therapy. J Clin
Oncol.
2011:29;2121-27.
9. Ellison G, et al. EGFR Mutation Testing in Lung Cancer: A Review
of Available Methods and Their Use for Analysis of Tumour Tissue
and Cytology Samples. J Clin
Pathol.
2013:66;79-89.
10. Pakkala,
S, et
al. Personalized Therapy for
Lung Cancer: Striking a Moving Target. JCI Insight. 2018;3(15):e120858.
Adrian Kemp
Company Secretary
AstraZeneca PLC
SIGNATURES
Pursuant
to the requirements of the Securities Exchange Act of 1934, the
Registrant has duly caused this report to be signed on its behalf
by the undersigned, thereunto duly authorized.
Date:
30 March
2020
|
By: /s/
Adrian Kemp
|
|
Name:
Adrian Kemp
|
|
Title:
Company Secretary
|