a1713n
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 May 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.
Enhertu US
Breakthrough status for lung cancer
18 May 2020 07:00 BST
Enhertu granted Breakthrough
Therapy Designation in the US for HER2-mutant metastatic
non-small cell lung cancer
Third Breakthrough Therapy Designation for Enhertu
AstraZeneca and Daiichi Sankyo Company, Limited (Daiichi
Sankyo)'s Enhertu (trastuzumab deruxtecan) has been granted
Breakthrough Therapy Designation (BTD) in the US for the treatment
of patients with metastatic non-small cell lung cancer (NSCLC)
whose tumours have a HER2 mutation and with disease progression on
or after platinum-based therapy.
NSCLC is the most common type of lung cancer, and prognosis is
particularly poor for patients with metastatic disease as only
about 6-10% will be alive five years after
diagnosis.1,2 Approximately
2-4% of patients with NSCLC have a HER2
mutation.3,4
The Food and Drug Administration (FDA)'s BTD is designed to
accelerate the development and regulatory review of potential new
medicines that are intended to treat a serious condition and
address a significant unmet medical need. The new medicine needs to
have shown encouraging early clinical results that demonstrate
substantial improvement on a clinically significant endpoint over
available medicines.
José Baselga, Executive Vice President, R&D Oncology,
said: "Today's news is very welcome as we continue to evaluate the
potential of Enhertu to help patients with this devastating type
of lung cancer. Targeted treatments and immunotherapies are
demonstrating tremendous advancements, but there remains an unmet
medical need for patients with HER2 mutations who are not
benefiting from such therapies or for those whose cancer continues
to progress."
Gilles Gallant, Senior Vice President, Global Head, Oncology
Development, Oncology R&D, Daiichi Sankyo, said: "We are
encouraged by the promising evidence of activity seen
with Enhertu in patients with advanced lung cancer and a
HER2 mutation. We look forward to working closely with the FDA on
the potential for Enhertu to become the first HER2-directed therapy
approved for non-small cell lung cancer."
The FDA granted BTD based on data from the ongoing Phase II
DESTINY-Lung01 trial currently testing Enhertu, a HER2-directed antibody drug conjugate
(ADC), in patients with HER2-mutant (HER2m) metastatic NSCLC, and
data from the Phase I trial published in Cancer
Discovery.5
An interim analysis from DESTINY-Lung01 will be presented during
the 2020 American Society of Clinical Oncology ASCO20 Virtual
Scientific Program, 29 to 31 May 2020.
The overall safety and tolerability profile
of Enhertu in the ongoing DESTINY-Lung01 trial is
consistent with that seen in the Phase I trial. The most common
adverse events to date (n=42) are gastrointestinal and
haematological including nausea, alopecia, anaemia, decreased
appetite and decreased neutrophil count. There have been five cases
of drug-related interstitial lung disease (ILD) and pneumonitis in
patients with HER2m NSCLC, all of which were Grade 2. There have
been no ILD-related deaths.
This is the third BTD granted
for Enhertu in
the US. Last week, Enhertu received BTD in patients with HER2-positive unresectable
or metastatic gastric or gastroesophageal junction adenocarcinoma
who have received two or more prior regimens including
trastuzumab. Enhertu received
BTD in 2017 for HER2-positive metastatic breast cancer and
received approval in
December 2019.
HER2
HER2 is a tyrosine kinase receptor growth-promoting protein
expressed on the surface of many types of tumours. In some
tumours, HER2 overexpression is associated with a specific HER2
gene alteration known as amplification and is often associated with
aggressive disease and poorer prognosis.6
Other HER2 gene alterations (called HER2 mutations) have been
identified in NSCLC, specifically adenocarcinomas, as distinct
molecular targets.4,7 Approximately
2-4% of patients with NSCLC have HER2 mutations, which have been
independently associated with cancer cell growth and poor
prognosis.3,4,7
NSCLC
Lung cancer is the leading cause of cancer death among both men and
women and accounts for about one-fifth of all cancer
deaths.8 In
the US, it is estimated that 228,820 new cases of lung cancer will
be diagnosed in 2020 and more than 135,000 people will die from the
disease.9
Lung cancer is broadly split into NSCLC and small cell lung cancer,
with 80-85% classified as NSCLC. 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. Stage IV is the most advanced form of
lung cancer and is often referred to as metastatic
disease.10 For
these patients with metastatic disease, prognosis is particularly
poor, as only 6-10% will be alive five years after
diagnosis.1,2 The
introduction of targeted therapies and checkpoint inhibitors in
recent years has improved outcomes for patients with advanced
NSCLC; however, new approaches are needed for those who are not
eligible for available treatments, or whose cancer continues to
progress.11 Currently,
no medicine is specifically approved for patients with HER2m
NSCLC.
DESTINY-Lung01
DESTINY-Lung01 is a global, Phase II, open-label, multicentre,
two-cohort trial assessing the safety and efficacy
of Enhertu in 170 patients with HER2m (n=90) or
HER2-overexpressing, defined as IHC 3+ or IHC 2+, (n=80)
unresectable and metastatic non-squamous NSCLC whose cancer has
progressed after one or more systemic therapies (including
chemotherapy, molecular targeted therapy or immunotherapy). The
primary endpoint is ORR. Key secondary endpoints include duration
of response, disease control rate, progression-free survival and
overall survival.12
Enhertu
Enhertu (trastuzumab
deruxtecan; fam-trastuzumab deruxtecan-nxki in the US) is a
HER2-directed ADC and is the lead ADC in the oncology portfolio of
Daiichi Sankyo and the most advanced programme in AstraZeneca's ADC
scientific platform. ADCs are targeted cancer medicines that
deliver cytotoxic chemotherapy ("payload") to cancer cells via a
linker attached to a monoclonal antibody that binds to a specific
target expressed on cancer cells.
Enhertu is approved in the
US and Japan for the treatment of adult patients with unresectable
or metastatic HER2-positive breast cancer who have received two or
more prior anti-HER2-based regimens based on the DESTINY-Breast01
trial.
Enhertu clinical
development
A comprehensive development programme is underway globally with six
registrational trials evaluating the efficacy and safety
of Enhertu monotherapy across multiple HER2-driven
cancers including breast, gastric and lung cancers. Trials in
combination with other anticancer treatments, such as
immunotherapy, are also underway.
Collaboration between AstraZeneca and Daiichi Sankyo
In March 2019, AstraZeneca and Daiichi Sankyo entered into a global
collaboration to jointly develop and
commercialise Enhertu worldwide, except in Japan where Daiichi
Sankyo maintains exclusive rights. Daiichi Sankyo is solely
responsible for manufacturing and supply.
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 histology,
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 FLAURA2.13-15 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 ADC is in development for HER2m metastatic
non-squamous NSCLC including trials in combination with other
anticancer medicines.12
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.16 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 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 investment 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 ADCs - 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 & 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. Goldstraw P, et al. The IASLC Lung
Cancer Staging Project: Proposals for Revision of the TNM Stage
Groupings in the Forthcoming (Eighth) Edition of the TNM
Classification for Lung Cancer. J Thorac
Oncol. 2016;
11(1):39-51.
2. American Cancer
Society. Lung Cancer. Early Detection, Diagnosis and Staging.
Accessed from: https://www.cancer.org/cancer/lung-cancer/detection-diagnosis-staging/survival-rates.html.
3. Campbell JD, et al. Distinct
patterns of somatic genome alterations in lung adenocarcinomas and
squamous cell carcinomas. Nat Genet. 2016 Jun; 48(6):607-16.
4. Li BT, et al. HER2 amplification
and HER2 mutation are distinct molecular targets in lung
cancers. J Thorac
Oncol. 2016 Mar; 11(3):
414-419.
5. Tsurutani, J et al. Targeting HER2
with Trastuzumab Deruxtecan: A Dose-Expansion, Phase I Study in
Multiple Advanced Solid Tumors. Cancer
Discov. 2020;
10(5).
6. Iqbal N, Iqbal N. Human Epidermal
Growth Factor Receptor 2 (HER2) in Cancers: Overexpression and
Therapeutic Implications. Mol Biol
Int. 2014; 2014:852748.
doi:10.1155/2014/852748.4.
7. Pillai RN, et al. HER2 mutations in
lung adenocarcinomas: A report from the Lung Cancer Mutation
Consortium. Cancer. 2017 Nov
1;123(21);4099-4105.
8. Bray F, et al. Global cancer
statistics 2018: GLOBOCAN estimates of incidence and mortality
worldwide for 36 cancers in 185 countries. CA Cancer J.
Clin. 2018;
68:394-424.6.
9. American Cancer
Society. Lung Cancer: Key Statistics for Lung Cancer. Accessed
from: https://www.cancer.org/cancer/lung-cancer/about/key-statistics.html.
10. American Cancer Society. Lung
Cancer: Non-Small Cell Lung Cancer Stages. Accessed
from: https://www.cancer.org/cancer/lung-cancer/detection-diagnosis-staging/staging-nsclc.html.
11. Economopoulou P, et al. The emerging
treatment landscape of advanced non-small cell lung
cancer. Ann Transl
Med 2018 Apr;
6(8):138.
12. ClinicalTrials.gov.
NCT03505710. Available at: https://www.clinicaltrials.gov/ct2/show/NCT03505710?term=ds-8201&cond=Nsclc&draw=1&rank=1
13. 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.
14. 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.
15. 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.
16. 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:
18 May 2020
|
By: /s/
Adrian Kemp
|
|
Name:
Adrian Kemp
|
|
Title:
Company Secretary
|