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
Indicate
by check mark whether the registrant files or will file annual
reports under cover of Form 20-F or Form 40-F.
Form
20-F X Form 40-F __
Indicate
by check mark if the registrant is submitting the Form 6-K in paper
as permitted by Regulation S-T Rule 101(b)(1):
Indicate
by check mark if the registrant is submitting the Form 6-K in paper
as permitted by Regulation S-T Rule 101(b)(7): ______
Indicate
by check mark whether the registrant by furnishing the information
contained in this Form is also thereby furnishing the information
to the Commission pursuant to Rule 12g3-2(b) under the Securities
Exchange Act of 1934.
Yes __
No X
If
“Yes” is marked, indicate below the file number
assigned to the Registrant in connection with Rule 12g3-2(b):
82-_____________
AstraZeneca PLC
INDEX
TO EXHIBITS
1.
Tagrisso
demonstrated unprecedented disease-free survival in the adjuvant
treatment of Stage IB-IIIA patients with EGFR-mutated lung
cancer
28 May 2020 22:00 BST
Tagrisso demonstrated
unprecedented disease-free survival in the adjuvant treatment
of Stage IB-IIIA patients with EGFR-mutated lung
cancer
Phase III ADAURA trial showed treatment with Tagrisso after surgery
with
curative intent reduced the risk of disease recurrence or death by
c. 80%
Detailed results from the Phase III ADAURA trial showed
AstraZeneca's Tagrisso (osimertinib) demonstrated a statistically
significant and clinically meaningful improvement in disease-free
survival (DFS) in 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.
Results will be presented during the plenary session of the
American Society of Clinical Oncology ASCO20 Virtual Scientific
Program on 31 May (abstract #LBA5).
In the primary endpoint of DFS in patients with Stage II and IIIA
disease, adjuvant treatment (after surgery)
with Tagrisso reduced the risk of disease recurrence or
death by 83% (based on a hazard ratio [HR] of 0.17; 95% confidence
interval [CI] 0.12, 0.23; p<0.0001). DFS results in the overall
trial population, Stage IB through IIIA, a key secondary endpoint,
demonstrated a reduction in the risk of disease recurrence or death
of 79% (based on a HR of 0.21; 95% CI 0.16, 0.28;
p<0.0001).
At two years, 89% of patients in the trial treated
with Tagrisso remained alive and disease free versus 53%
on placebo. Consistent DFS results were seen across all subgroups,
including patients who were treated with surgery followed by
chemotherapy and those who received surgery only, as well as in
Asian and non-Asian patients.
Roy S. Herbst, MD, Ph.D., chief of Medical Oncology at Yale Cancer
Center and Smilow Cancer Hospital, New Haven, CT and principal
investigator in the Phase III ADAURA trial, said: "These data are
transformative for patients with early-stage EGFR-mutated non-small
cell lung cancer who face high rates of recurrence even after
successful surgery and subsequent treatment with adjuvant
chemotherapy. Tagrisso will provide a much-needed new treatment
option that has the potential to change the practice of medicine
and improve outcomes for patients in this
setting."
José Baselga, Executive Vice President, Oncology R&D,
said: "The momentous results of the Phase III ADAURA trial
for Tagrisso demonstrate for the first time in a global
trial that an EGFR inhibitor can change the course of early-stage
EGFR-mutated lung cancer and provide hope for a cure. We are
discussing these outstanding data with regulatory authorities and
look forward to bringing the benefits of Tagrisso to patients with early-stage
disease."
In April
2020, an Independent Data
Monitoring Committee recommended for the Phase III ADAURA trial to
be unblinded two years early based on its determination of
overwhelming efficacy. At the time of data cut-off, overall
survival (OS) data favoured Tagrisso, but were not mature. The trial will continue to
assess OS as a secondary endpoint.
Summary of ADAURA results
|
Tagrisso
|
Placebo
|
DFS Stages II-IIIA (primary endpoint)i
|
(n=233)
|
(n=237)
|
HR (95%
CI)
|
0.17
(0.12, 0.23)
|
p-value
|
p<0.0001
|
DFS rates (95%
CI)
|
|
|
One year
|
97%
(94%, 99%)
|
61%
(54%, 67%)
|
Two years
|
90%
(84%, 93%)
|
44%
(37%, 51%)
|
Three years
|
80%
(68%, 88%)
|
28%
(19%, 38%)
|
DFS Stages IB-IIIA (secondary endpoint)i
|
(n=339)
|
(n=343)
|
HR (95%
CI)
|
0.21
(0.16, 0.28)
|
p-value
|
p<0.0001
|
DFS
rates (95% CI)
|
|
|
One year
|
97%
(95%, 99%)
|
69%
(63%, 73%)
|
Two years
|
89%
(84%, 92%)
|
53%
(47%, 59%)
|
Three years
|
79%
(69%, 86%)
|
41%
(33%, 49%)
|
i The data cut-off date for DFS was 17 January 2020.
The safety and tolerability of Tagrisso in this trial was consistent with previous
trials in the metastatic setting. Adverse events at Grade 3 or
higher from all causes occurred in 10% of patients in
the Tagrisso arm versus 3% in the placebo arm as assessed
by the investigator.
Tagrisso is approved for
the 1st-line treatment of patients with locally advanced or
metastatic EGFRm NSCLC in the US, Japan, China, the EU and
many other countries around the world.
Several presentations featured during the ASCO20 Virtual Scientific
Program will showcase AstraZeneca's
leadership in lung cancer across early and late-stage disease and
reinforce the Company's biomarker-driven
approach.
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.1 Lung
cancer is broadly split into NSCLC and small cell lung cancer, with
80-85% classified as NSCLC.2 A
significant portion of patients with resectable NSCLC eventually
develop recurrence despite surgery (complete
resection).3,4 Approximately
10-15% of NSCLC patients in the US and Europe, and 30-40% of
patients in Asia have EGFRm NSCLC.5-7 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.8 Approximately
25-30% of patients with NSCLC present with resectable disease at
diagnosis.9-11
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 with 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 is
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 as a secondary endpoint.
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. Tagrisso is also being developed in the Stage III,
unresectable setting (LAURA), 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 EU and 30-40% of NSCLC patients in
Asia, with the approved medicines Iressa (gefitinib) and Tagrisso, and its ongoing Phase III trials LAURA, and
FLAURA2.5-7
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 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.12 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 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 & 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. World Health Organization. International Agency for Research on
Cancer. Globocan Worldwide Fact Sheet 2018. Available
at http://globocan.iarc.fr/Pages/fact_sheets_population.aspx Accessed:
May 2020.
2. LUNGevity Foundation. Types of Lung Cancer. Available
at https://www.lungevity.org/about-lung-cancer/lung-cancer-101/types-of-lung-cancer Accessed:
May 2020.
3. Sasaki H, et al. Prognosis of recurrent non-small cell lung
cancer following complete resection. Onc
Letters. 2014:7;1300-1304.
4. 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.
5. 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.
6. 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.
7. 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.
8. 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.
9. Cagle P, et al. Lung Cancer Biomarkers: Present Status and
Future Developments. Archives Pathology Lab
Med.
2013;137:1191-1198.
10. Datta D, et al. Preoperative Evaluation of Patients
Undergoing Lung Resection Surgery. Chest. 2003;123: 2096-2103.
11. Le Chevalier T. Adjuvant chemotherapy for resectable
non-small-cell lung cancer: where is it
going? Ann Oncol. 2010;21:196-8.
12. 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:
29 May
2020
|
By: /s/
Adrian Kemp
|
|
Name:
Adrian Kemp
|
|
Title:
Company Secretary
|