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 July
2020
Commission
File Number: 001-11960
AstraZeneca PLC
1
Francis Crick Avenue
Cambridge
Biomedical Campus
Cambridge
CB2 0AA
United
Kingdom
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by check mark whether the registrant files or will file annual
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to the Commission pursuant to Rule 12g3-2(b) under the Securities
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AstraZeneca PLC
INDEX
TO EXHIBITS
1.
Tagrisso US BTD for
EGFRm adjuvant lung cancer
30 July 2020 07:05 BST
Tagrisso granted Breakthrough Therapy Designation in
the US for the
adjuvant treatment of patients with Stage IB-IIIA EGFR-mutated lung
cancer
Designation based on unprecedented results from the Phase III
ADAURA trial
where Tagrisso reduced the risk of disease recurrence or death by
c. 80%
AstraZeneca's Tagrisso (osimertinib) has been granted Breakthrough
Therapy Designation (BTD) in the US for the adjuvant treatment of
patients with early-stage (IB, II and IIIA) epidermal growth factor
receptor-mutated (EGFRm) non-small cell lung cancer (NSCLC) after
complete tumour resection with curative intent.
The Food and Drug Administration's (FDA) 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.
While up to 30% of patients with NSCLC may be diagnosed early
enough to have potentially curative surgery, disease recurrence is
common in early-stage disease and nearly half of patients diagnosed
in Stage IB, and over three quarters of patients diagnosed in Stage
IIIA, experience recurrence within five years.1-6
José Baselga, Executive Vice President, Oncology R&D
said: "Patients with early-stage EGFRm lung cancer often
experience recurrence even after successful surgery and adjuvant
chemotherapy, yet there are currently no approved targeted
treatments to improve outcomes. The Phase III ADAURA trial
with Tagrisso demonstrated an unprecedented level of
clinical benefit in these patients, and we are working closely with
the FDA to deliver this potentially curative treatment to patients
as quickly as possible."
The FDA granted the BTD based on data from the Phase III ADAURA
trial, which were also recently
presented during the
plenary session of the American Society of Clinical Oncology ASCO20
Virtual Scientific Program.
In the trial Tagrisso demonstrated a statistically significant and
clinically meaningful improvement in disease-free survival (DFS) in
the adjuvant treatment of Stage IB-IIIA EGFRm NSCLC patients,
reducing the risk of disease recurrence or death by 79% (HR 0.21;
95% CI 0.16-0.28; p<0.0001) in a key secondary endpoint.
In April
2020, an Independent Data Monitoring Committee
recommended for the trial to be unblinded two years early based on
its determination of overwhelming efficacy.
Tagrisso is approved for
the 1st-line treatment of patients with locally advanced or
metastatic EGFRm NSCLC and for the treatment of locally advanced or
metastatic EGFR T790M mutation-positive NSCLC in the US, Japan,
China, the EU and many other countries around the
world.
Lung cancer
Lung cancer is the leading cause of cancer death among both men and
women, accounting for about one-fifth of all cancer
deaths.7 Lung
cancer is broadly split into NSCLC and small cell lung cancer, with
80-85% classified as NSCLC.8 The
majority of all NSCLC patients are diagnosed with advanced disease
while approximately 25-30% present with resectable disease at
diagnosis.1-3 A
significant portion of patients with resectable NSCLC eventually
develop recurrence despite complete tumour resection and adjuvant
chemotherapy. Approximately 10-15% of NSCLC patients in the US and
Europe, and 30-40% of patients in Asia have EGFRm
NSCLC.9-11 These
patients are particularly sensitive to treatment with EGFR-tyrosine
kinase inhibitors (TKIs) which block the cell-signalling pathways
that drive the growth of tumour cells.12
ADAURA
ADAURA is a randomised, double-blinded, global, placebo-controlled
Phase III trial in the adjuvant treatment of 682 patients with
Stage IB, II, IIIA EGFRm NSCLC following complete tumour resection
and adjuvant chemotherapy as indicated. In the experimental arm,
patients were treated with Tagrisso 80mg once-daily oral tablets for three years
or until disease recurrence. The trial enrolled in more than 200
centres across more than 20 countries, including the US, in Europe,
South America, Asia and the Middle East. The primary endpoint DFS
in Stage II and IIIA patients and a key secondary endpoint is DFS
in Stage IB, II and IIIA patients. The data readout was originally
anticipated in 2022. The trial will continue to assess
OS.
Tagrisso
Tagrisso (osimertinib) is
a third-generation, irreversible EGFR-TKI with clinical activity
against CNS metastases. Tagrisso 40mg and 80mg once-daily oral tablets have
received approval in the US, Japan, China, the EU and many
countries around the world for 1st-line EGFRm advanced NSCLC and
EGFR T790M mutation-positive advanced
NSCLC. Tagrisso is also being developed in the Stage III,
unresectable setting (LAURA), in the neoadjuvant resectable setting
(NeoADAURA), in combination with chemotherapy (FLAURA2) and in
combination with potential new medicines to address resistance to
EGFR-TKIs (SAVANNAH, ORCHARD).
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.
AstraZeneca aims to address the unmet needs of patients with EGFRm
tumours as a genetic driver of disease, which occur in 10-15% of
NSCLC patients in the US and the EU and 30-40% of NSCLC patients in
Asia, with the approved medicines Iressa (gefitinib) and Tagrisso, and its ongoing Phase III trials LAURA,
NeoADAURA, and FLAURA2.9-11
AstraZeneca is 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 (ADC) is in development for metastatic
non-squamous HER2-overexpressing or HER2-mutated NSCLC including
trials in combination with other anticancer treatments. In
addition, DS-1062, a trophoblast cell-surface antigen 2
(TROP2)-directed ADC, is in early development for advanced NSCLC
where TROP2 is overexpressed in the majority of
patients.13
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.14 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 MERMAID-1, 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
trials NeoCOAST, COAST and HUDSON in combination with potential new
medicines from the early-stage pipeline
including Enhertu.
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 seven
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.
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 & 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. Cagle P, et al. Lung Cancer Biomarkers: Present Status and
Future Developments. Archives Pathology Lab
Med. 2013;137:1191-1198.
2. Le Chevalier T. Adjuvant Chemotherapy for Resectable
Non-Small-Cell Lung Cancer: Where is it
Going? Ann Oncol. 2010;21:196-8.
3. Datta D, et al. Preoperative Evaluation of Patients
Undergoing Lung Resection Surgery. Chest. 2003;123: 2096-2103.
4. Sasaki H, et al. Prognosis of Recurrent Non-Small Cell Lung
Cancer Following Complete Resection. Onc
Letters. 2014:7;1300-1304.
5. Fink-Neuboeck N, et
al. Hazards of Recurrence,
Second Primary, or Other Tumor at Ten Years After Surgery for
Non-Small-Cell Lung Cancer. Clinical Lung
Cancer.
February 25 2020. https://doi.org/10.1016/j.cllc.2020.02.011.
6. Pignon et al. Lung Adjuvant Cisplatin Evaluation: A Pooled
Analysis by the LACE Collaborative Group. J Clin
Oncol 2008;26:3552-3559.
7. 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.
Accessed July 2020.
8. LUNGevity Foundation. Types of Lung Cancer. Available
at https://www.lungevity.org/about-lung-cancer/lung-cancer-101/types-of-lung-cancer.
Accessed July 2020.
9. 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.
10. 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.
11. 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.
12. Cross DA, et al. AZD9291, an Irreversible EGFR TKI, Overcomes
T790M-Mediated Resistance to EGFR Inhibitors in Lung
Cancer. Cancer
Discov.
2014;4(9):1046-1061.
13. Zaman S, et al. Targeting Trop-2 in solid tumors: future
prospects. Onco Targets
Ther. 2019; 12:
1781-1790.
14. 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 July 2020
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By: /s/
Adrian Kemp
|
|
Name:
Adrian Kemp
|
|
Title:
Company Secretary
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