Blueprint
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 June
2019
Commission
File Number: 001-11960
AstraZeneca PLC
1
Francis Crick Avenue
Cambridge
Biomedical Campus
Cambridge
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United
Kingdom
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AstraZeneca PLC
INDEX
TO EXHIBITS
1.
Calquence
significantly prolonged the time patient
17 June 2019 07:00 BST
Calquence significantly
prolonged the time patients lived without disease
progression in relapsed or refractory chronic lymphocytic
leukaemia
An encouraging 88% of patients on Calquence remained free of
disease progression after 12 months, vs. 68% of
patients on rituximab combined with idelalisib or
bendamustine
AstraZeneca today announced detailed results from the interim
analysis of the Phase III ASCEND trial at
the European Hematology Association (EHA) Annual Congress in
Amsterdam, showing Calquence (acalabrutinib) significantly prolonged the
time patients live without disease progression in relapsed or
refractory chronic lymphocytic leukaemia (CLL).
The ASCEND trial compared Calquence with the physician's choice of rituximab
combined with idelalisib (IdR) or bendamustine (BR) in patients
with relapsed or refractory CLL.
At a median follow-up of 16.1 months, results from the trial showed
a statistically-significant and clinically-meaningful improvement
in progression-free survival (PFS) for patients treated
with Calquence vs. IdR or BR, reducing the risk of
disease progression or death by 69% (HR, 0.31; 95%
CI, 0.20-0.49,
p<0.0001). The
median time without disease progression for patients treated
with Calquence has not yet been reached vs. 16.5 months in
the control arm. At 12 months, 88% of patients
on Calquence showed no disease progression compared to
68% for the control arm. The safety and tolerability
of Calquence was consistent with its established
profile.
José Baselga, Executive Vice President, Oncology R&D said:
"These data add to the growing body of evidence to support the
profile of Calquence as a selective BTK inhibitor that offers a
chemotherapy-free treatment option with a favourable safety profile
in chronic lymphocytic leukaemia, a life-threatening disease.
These data, along with our recent positive results from the Phase
III ELEVATE-TN trial in previously-untreated chronic lymphocytic
leukaemia, will serve as the foundation for regulatory submissions
later this year."
Paolo Ghia, MD, Professor, Medical Oncology, Università
Vita-Salute San Raffaele in Milan, and investigator of the ASCEND
trial, said: "This is the first randomised trial to directly
compare a BTK inhibitor as monotherapy with standard
chemoimmunotherapy or idelalisib and rituximab combinations. With a
significant improvement in progression-free survival and a
favourable safety profile, acalabrutinib may become an important
choice for the treatment of patients with relapsed or refractory
chronic lymphocytic leukaemia."
Kaplan-Meier plot for PFS as assessed by an independent review
committee in the intent-to-treat population1
Link to
graph: http://www.rns-pdf.londonstockexchange.com/rns/4350C_1-2019-6-17.pdf
Safety overview
Most
common (≥15%)
AEs,
n (%)
|
Calquence(n=154)
|
IdR(n=118)
|
BR(n=35)
|
Any
|
Grade
≥3
|
Any
|
Grade
≥3
|
Any
|
Grade
≥3
|
Headache
|
34
(22%)
|
1
(1%)
|
7
(6%)
|
0
|
0
|
0
|
Neutropenia
|
30
(19%)
|
24
(16%)
|
53
(45%)
|
47
(40%)
|
12
(34%)
|
11
(31%)
|
Diarrhoea
|
28
(18%)
|
2
(1%)
|
55
(47%)
|
28
(24%)
|
5
(14%)
|
0
|
Anaemia
|
23
(15%)
|
18
(12%)
|
11
(9%)
|
8
(7%)
|
4
(11%)
|
3
(9%)
|
Cough
|
23
(15%)
|
0
|
18
(15%)
|
1
(1%)
|
2
(6%)
|
0
|
Pyrexia
|
19
(12%)
|
1
(1%)
|
21
(18%)
|
8
(7%)
|
6
(17%)
|
1
(3%)
|
Fatigue
|
15
(10%)
|
2
(1%)
|
10
(8%)
|
0
|
8
(23%)
|
1(3%)
|
Nausea
|
11
(7%)
|
0
|
15
(13%)
|
1
(1%)
|
7
(20%)
|
0
|
IRR
|
0
|
0
|
9
(8%)
|
2
(2%)
|
8
(23%)
|
1
(3%)
|
Events
of clinical interest for Calquence
|
Atrial
fibrillation
|
8
(5%)
|
2
(1%)
|
4
(3%)
|
1
(1%)
|
1
(3%)
|
1
(3%)
|
Bleeding
|
40
(26%)
|
3
(2%)
|
9
(8%)
|
3
(3%)
|
2
(6%)
|
1(3%)
|
Hypertension
|
5
(3%)
|
3
(2%)
|
5
(4%)
|
1
(1%)
|
0
|
0
|
SPM*
excluding NMSC**
|
10
(6%)
|
5
(3%)
|
3
(3%)
|
0
|
1
(3%)
|
1
(3%)
|
*Secondary primary malignancy **Non-melanoma skin
cancer.
AstraZeneca recently announced that
the Phase III ELEVATE-TN trial met its primary endpoint at
interim analysis in patients with previously-untreated CLL and
that full results will be reported at a forthcoming medical
meeting. Calquence is currently approved for the treatment of
adults with relapsed or refractory mantle cell lymphoma (MCL) in
the US, Brazil, the United Arab Emirates, and Qatar and is being
developed for the treatment of CLL and other blood
cancers.
About ASCEND
ASCEND (ACE-CL-309) is a global, randomised, multicentre,
open-label Phase III trial evaluating the efficacy
of Calquence in previously-treated patients with
CLL.2 In
the trial, 310 patients were randomised (1:1) into two arms.
Patients in the first arm received Calquence monotherapy (100mg twice daily until disease
progression). Patients in the second arm received physician's
choice of either rituximab in combination with idelalisib or
rituximab in combination with bendamustine.1,2
The primary endpoint is PFS assessed by an independent review
committee (IRC), and key secondary endpoints include
physician-assessed PFS, IRC- and physician-assessed overall
response rate (ORR) and duration of response (DoR), as well as
overall survival (OS), patient reported outcomes (PROs) and time to
next treatment (TTNT).1,2
About Calquence
Calquence (acalabrutinib)
was granted accelerated approval by the US Food and Drug
Administration (FDA) in October 2017 for the treatment of adult
patients with MCL who have received at least one prior therapy.
Continued approval for this indication may be contingent upon
verification and description of clinical benefit in confirmatory
trials.
Calquence is an inhibitor
of Bruton tyrosine kinase (BTK). Calquence binds covalently to BTK, thereby inhibiting
its activity.3 In
B-cells, BTK signalling results in activation of pathways necessary
for B-cell proliferation, trafficking, chemotaxis, and
adhesion.
As part of an extensive clinical development programme, AstraZeneca
and Acerta Pharma are currently evaluating Calquence in 26 company-sponsored clinical
trials. Calquence is being developed for the treatment of
multiple B-cell blood cancers including CLL, MCL, diffuse large
B-cell lymphoma, Waldenstrom macroglobulinaemia, follicular
lymphoma, and multiple myeloma and other haematologic malignancies.
Beyond the positive Phase III trials ASCEND and ELEVATE-TN, other
Phase III trials in CLL are ongoing, including ELEVATE-RR
(ACE-CL-006) evaluating acalabrutinib vs. ibrutinib in patients
with previously-treated high-risk CLL, and ACE-CL-311 evaluating
acalabrutinib in combination with venetoclax and with/without
obinutuzumab in patients with previously-untreated CLL without 17p
deletion or TP53 mutation.
About chronic lymphocytic leukaemia
Chronic lymphocytic leukaemia (CLL) is the most common type of
leukaemia in adults, with an estimated 191,000 new cases globally
and 20,720 new cases in the US annually, and prevalence that is
expected to grow with improved treatment.4-7 In
CLL, too many blood stem cells in the bone marrow become abnormal
lymphocytes and these abnormal cells have difficulty fighting
infections.4 As
the number of abnormal cells grows there is less room for healthy
white blood cells, red blood cells and
platelets.4 This
could result in anaemia, infection and bleeding.4 B-cell
receptor signalling through BTK is one of the essential growth
pathways for CLL.
About AstraZeneca in haematology
Leveraging its strength in oncology, AstraZeneca has established
haematology as one of four key oncology disease areas of focus. The
Company's haematology franchise includes two US FDA-approved
medicines and a robust global development programme for a broad
portfolio of potential blood cancer treatments. Acerta Pharma
serves as AstraZeneca's haematology research and development arm.
AstraZeneca partners with like-minded science-led companies to
advance the discovery and development of therapies to address unmet
need.
In October 2018, AstraZeneca and Innate
Pharma announced a global
strategic collaboration that included Innate
Pharma licensing the US
commercial rights of Lumoxiti (moxetumomab pasudotox-tdfk), and with
support from AstraZeneca, will continue EU development and
commercialisation, pending regulatory submission and
approval.
About 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 at
least six new medicines to be launched between 2014 and 2020, and a
broad pipeline of small molecules and biologics in development, we
are committed to advance oncology as a key growth driver for
AstraZeneca focused on lung, ovarian, breast and blood cancers. In
addition to our core capabilities, we actively pursue innovative
partnerships and investments that accelerate the delivery of our
strategy as illustrated by our 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.
About AstraZeneca
AstraZeneca 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. AstraZeneca operates in over 100
countries and its innovative medicines are used by millions of
patients worldwide. For more information, please
visit www.astrazeneca.com and
follow us on Twitter @AstraZeneca.
Media
Relations
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+44 203
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+44 203
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Adrian Kemp
Company Secretary
AstraZeneca PLC
References
1 Ghia P, Pluta A, Wach M, et al. ASCEND Phase 3 study of
acalabrutinib vs. investigator's choice of rituxumab plus
idelalisib (idR) or bendamustine (BR) in patients with
relapsed/refractory chronic lymphocytic leukaemia (CLL). Abstract
LB2606 at: European Hematology Association 2019 Annual Meeting.
Available online. Accessed June 2019.
2 ClinicalTrials.gov. A Study of Acalabrutinib vs Investigator's
Choice of Idelalisib Plus Rituximab or Bendamustine Plus Rituximab
in R/R CLL. NCT02970318. Available online. Accessed June
2019.
3 CALQUENCE® (acalabrutinib)
Prescribing Information. AstraZeneca Pharmaceuticals LP,
Wilmington, DE.
4 National Cancer Institute. Chronic Lymphocytic Leukaemia
Treatment (PDQ®)-Patient Version. Available online. Accessed
June 2019.5Global Burden of Disease Cancer Collaboration. JAMA
Oncol. 2017;3(4):524-528.
5 Global Burden of Disease Cancer Collaboration. JAMA Oncol.
2017;3(4):524-52.
6 National Institute of Health SEER Program. Cancer Stat Facts:
Leukemia-Chronic Lymphocytic Leukemia (CLL). Available online.
Accessed June 2019.
7 Jain N, et al. Prevalence and Economic Burden of Chronic
Lymphocytic Leukemia (CLL) in the Era of Oral Targeted Therapies.
Blood. 2015;126:871.
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:
17 June
2019
|
By: /s/
Adrian Kemp
|
|
Name:
Adrian Kemp
|
|
Title:
Company Secretary
|