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 November
2019
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.
Calquence
data to show improved progression-free survival in Phase III
front-line chronic lymphocytic leukaemia trial at ASH 2019 Annual
Meeting
6 November 2019 14:00 GMT
Calquence data to show improved progression-free
survival in Phase III front-line chronic lymphocytic leukaemia
trial at ASH 2019 Annual Meeting
Robust early-stage pipeline advancements and presentations across
multiple scientific platforms demonstrate potential to
improve
treatment outcomes in blood cancers with high unmet
need
AstraZeneca will present the first data from the Phase III
ELEVATE-TN trial assessing Calquence (acalabrutinib), a next-generation selective
Bruton's tyrosine kinase (BTK) inhibitor, in patients with
previously untreated chronic lymphocytic leukaemia (CLL), as well
as data from novel-combination trials across multiple blood cancers
at the 2019 American Society of Hematology (ASH) Annual Meeting and
Exposition in Orlando, USA, December 7-10.1
The Company will present over 30 abstracts, including seven
oral presentations, in CLL, mantle cell lymphoma (MCL), acute
myeloid leukaemia (AML), diffuse large B-cell lymphoma (DLBCL) and
multiple myeloma (MM). Key data include:
●
The first presentation of data from the
pivotal Phase III ELEVATE-TN
trial evaluating Calquence in combination with obinutuzumab
and Calquence monotherapy versus obinutuzumab combined
with chlorambucil chemotherapy in previously untreated
CLL
●
Long-term efficacy, safety and tolerability data
on Calquence in relapsed or refractory CLL from the Phase
I/II ACE-CL-001 trial
●
First-time
data on roxadustat as a potential new treatment for anaemia in
patients with primary myelodysplastic syndrome (MDS)
Dave Fredrickson, Executive Vice President, Oncology Business Unit
said: "AstraZeneca continues to demonstrate its strength in
haematology, presenting new research at ASH that spans targeted
therapies across eight blood cancers. This year we are especially
excited to present the ELEVATE-TN data demonstrating
the impressive efficacy and
tolerability of Calquence in 1st-line chronic lymphocytic
leukaemia."
Key headline data from
the Calquence Phase III ELEVATE-TN
trial
Efficacy measure
|
Calquence plus
obinutuzumab
N = 179
|
Calquence monotherapy
N = 179
|
Obinutuzumab plus chlorambucil
N = 177
|
Stratified analysis, median follow-up 28 months
|
Hazard ratio for PFS endpoint (vs. obinutuzumab +
chlorambucil), stratified
analysis
|
HR 0.10
(primary endpoint)
95% CI
0.06-0.17,
P<0.0001
median
not reached
|
HR 0.20
(secondary endpoint)
95% CI
0.13-0.30,
p<0.0001
median
not reached
|
n/a
median 22.6 months
|
Select adverse events (AEs) include infusion reactions, which were
less frequent with Calquence plus obinutuzumab (13%) than with
obinutuzumab plus chlorambucil (40%). Additionally, AEs led to
treatment discontinuation in 11% of patients
on Calquence plus obinutuzumab, 9% of patients
on Calquence, and 14% of patients on obinutuzumab plus
chlorambucil. With >2 y of follow-up, 79% of patients in both
the Calquence-containing arms remain
on Calquence as
a monotherapy. Other select AEs (Calquence plus obinutuzumab
or Calquence vs
chlorambucil plus obinutuzumab) included atrial fibrillation (any
grade: 3% or 4% vs. 1%), bleeding (any grade/Grade ≥3: 43%/2%
or 39%/2% vs. 12%/0%), and hypertension (Grade ≥3: 3% or 2%
vs. 3%).
Full data from the ELEVATE-TN trial will be presented at ASH by the
primary investigators. AstraZeneca has
submitted Calquence for US regulatory review in 1st-line and
relapsed/refractory CLL.
Raising the bar for CLL treatment
outcomes with Calquence
In addition to the oral presentation of the ELEVATE-TN results, key
presentations include:
●
An oral presentation on preliminary data from a
Phase II investigator-initiated trial
evaluating Calquence combined with obinutuzumab and venetoclax in
patients with previously untreated CLL, including high-risk disease
status and a trial-in-progress poster detailing an ongoing
Phase III trial to evaluate this novel combination in patients with
previously untreated CLL without del(17p)
or TP53 mutation.
●
Long-term (42-month) follow-up results from the
Phase I/II ACE-CL-001 trial confirming Calquence initial
efficacy from this trial for the treatment of relapsed or
refractory CLL and providing additional data on duration of
response and long-term tolerability.
Exploring a potential treatment option for a challenging
comorbidity in blood cancer
●
An oral presentation on first-time data from a
global Phase III trial evaluating roxadustat to treat anaemia in
patients with primary MDS. Considered a type of cancer, MDS
is a group of diverse bone marrow disorders in which the bone
marrow does not produce enough healthy blood
cells. Approximately one in
three MDS patients can progress to AML.2
Exploring potential new medicines from the pipeline and new
treatment strategies for aggressive or treatment-resistant blood
cancers
●
In AML, an oral presentation and four poster
presentations, including results from an Imfinzi (durvalumab) and azacitidine combination for
the 1st-line treatment of older, chemotherapy-ineligible patients
and data from a Phase I/II clinical trial of AZD2811(nanoparticles)
as a monotherapy or in combination with azacitidine in previously
untreated or relapsed/refractory patients who are not eligible for
intensive induction therapy.
●
In DLBCL, five abstracts, including a poster
presentation detailing the ongoing Phase I PRISM trial
of Calquence in
four different combinations with potential new medicines targeting
STAT3, ATR, CD47 and BRD4.
●
In MM, three poster presentations, including
results of a Phase I trial of MEDI2228, a BCMA antibody-PBD
conjugate and potential new medicine, as a monotherapy and in
combinations with bortezomib and DNA-damage response medicines and
results from an in vitro trial of AZD4785 alone or with proteasome
inhibitors targeting mutant KRAS.
Key AstraZeneca presentations at ASH 2019
|
|
|
|
|
Sharman, J.
|
ELEVATE
TN: Phase 3 Study of Acalabrutinib Combined with Obinutuzumab (O)
or Alone vs O Plus Chlorambucil (Clb) in Patients (Pts) With
Treatment-Naive Chronic Lymphocytic Leukemia (CLL)
|
Oral Presentation
Saturday 7 December
07:30 ET
Orange County Convention Center, Hall D
|
Lampson, BL.
|
Preliminary
Safety and Efficacy Results from a Phase 2 Study of Acalabrutinib,
Venetoclax and Obinutuzumab in Patients with Previously Untreated
Chronic Lymphocytic Leukemia (CLL)
|
Oral Presentation
Saturday 7 December
07:45 ET
Orange County Convention Center, Hall D
|
Frei, CR.
|
Treatment
Patterns and Outcomes of 1205 Patients on Novel Agents in the US
Veterans Health Administration (VHA) System: Results from
Retrospective EMR and Chart Review Study in the Real-World
Setting
|
Oral Presentation
Monday 9 December
15:15 ET
Orange County Convention Center, Valencia A (W415A)
|
Goyal, RK.
|
Overall
Survival, Adverse Events, and Economic Burden in Medicare Patients
with Chronic Lymphocytic Leukemia Receiving Cancer-Directed
Therapy
|
Oral Presentation
Monday 9 December
15:15 ET
Orange County Convention Center, Valencia A (W415A)
|
Furman, RR.
|
Acalabrutinib
Monotherapy in Patients with Relapsed/Refractory Chronic
Lymphocytic Leukemia: 42-Month Follow-Up of a Phase 2
Study
|
Poster
Presentation
Sunday
8 December
18:00 -
20:00 ET
Orange
County Convention Center, Hall B
|
Brown, JR.
|
A Phase
3 Trial Comparing the Efficacy and Safety of Acalabrutinib in
Combination with Venetoclax with or without Obinutuzumab, Compared
with Investigator's Choice of Chemoimmunotherapy in Patients with
Previously Untreated Chronic Lymphocytic Leukemia (CLL) without
del(17p) or TP53 Mutation
|
Poster Presentation
Monday 9 December
18:00 - 20:00 ET
Orange County Convention Center, Hall B
|
Mantle cell lymphoma
|
|
Kabadi, S.
|
Overall
Survival, Adverse Events, and Economic Burden in Medicare-Insured
Patients with Mantle Cell Lymphoma Receiving Cancer-Directed
Therapy
|
Oral Presentation
Saturday 7 December
08:00 ET
Orange County Convention Center, W308
|
Ryan, K.
|
Characteristics
of Mantle Cell Lymphoma (MCL) and Chronic Lymphocytic Leukemia
(CLL) Patients Treated with Acalabrutinib in a Real World Setting
in the United States
|
Poster Presentation
Sunday 8 December
18:00 - 20:00 ET
Orange County Convention Center, Hall B
|
Acute myeloid leukaemia
|
Zeidan, A.
|
Efficacy
and Safety of Azacitidine (AZA) in Combination with the Anti-PD-L1
Durvalumab (durva) for the Front-line Treatment of Older Patients
(pts) with Acute Myeloid Leukemia (AML) Who Are Unfit for Intensive
Chemotherapy (IC) and Pts with Higher-Risk Myelodysplastic
Syndromes (HR-MDS): Results from a Large, International, Randomized
Phase 2 Study
|
Oral
Presentation
Monday
9 December
16:30
ET
Orange
County Convention Center, Chapin Theater (W320)
|
Donnellan, W.
|
A Phase
I/II Study of AZD2811NP as Monotherapy or in Combination in
Treatment-Naïve or R/R AML/MDS Patients Not Eligible for
Intensive Induction Therapy
|
Poster Presentation
Monday 9 December
18:00 - 20:00 ET
Orange County Convention Center, Hall B
|
Diffuse large B-cell lymphoma
|
Roschewski, M.
|
PRISM:
A Platform Protocol for the Treatment of Relapsed/Refractory
Aggressive Non-Hodgkin Lymphoma
|
Poster Presentation
Sunday 8 December
18:00 - 20:00 ET
Orange County Convention Center, Hall B
|
Moskowitz, CH.
|
Safety
and Antitumor Activity Study of Loncastuximab Tesirine and
Durvalumab in Diffuse Large B-Cell, Mantle Cell, or Follicular
Lymphoma
|
|
Multiple myeloma
|
Xing, L.
|
Anti-BCMA
PBD MEDI2228 combats drug resistance and synergizes with bortezomib
and inhibitors to DNA damage response in multiple
myeloma
|
Poster Presentation
Saturday 7 December
17:30 - 19:30 ET
Orange County Convention Center, Hall B
|
Sacco, A.
|
Specific
targeting of KRAS using a novel high-affinity KRAS antisense
oligonucleotide in myeloma.
|
Poster Presentation
Sunday 8 December
18:00 - 20:00 ET
Orange County Convention Center, Hall B
|
Xing, L.
|
MEDI2228,
a novel BCMA antibody-PBD conjugate, sensitizes human multiple
myeloma cells to NK cell-mediated cytotoxicity and upregulates CD38
expression in MM cells: clinical implication
|
Poster Presentation
Sunday 8 December
18:00 - 20:00 ET
Orange County Convention Center, Hall B
|
Primary MDS-induced anaemia
|
|
Henry, D.
|
Roxadustat
(FG4592; ASP1517; AZD9941) in the Treatment of Anemia in Patients
with Lower Risk Myelodysplastic Syndrome (LR-MDS) and Low Red Blood
Cell (RBC) Transfusion Burden (LTB)
|
Oral Presentation
Monday 9 December
16:30 - 18:00 ET
Orange County Convention Center, W311ABCD
|
About ELEVATE-TN
ELEVATE-TN (ACE-CL-007) is a randomised, multicentre, open-label
Phase III trial evaluating the safety and efficacy
of Calquence in combination with obinutuzumab, a CD20
monoclonal antibody, or Calquence alone vs. chlorambucil, a chemotherapy, in
combination with obinutuzumab in previously untreated patients with
CLL. In the trial, 535 patients were
randomised (1:1:1) into three arms. Patients in the first arm
received chlorambucil in combination with obinutuzumab. Patients in
the second arm received Calquence (100mg twice daily until disease progression
or unacceptable toxicity) in combination with obinutuzumab.
Patients in the third arm received Calquence monotherapy (100mg twice daily until disease
progression or unacceptable toxicity).3
The primary endpoint is progression-free survival (PFS) in
the Calquence and obinutuzumab arm compared to the
chlorambucil and obinutuzumab arm, assessed by an independent
review committee (IRC), and a key secondary endpoint is
IRC-assessed PFS in the Calquence monotherapy arm compared to the chlorambucil
and obinutuzumab arm. Other secondary endpoints include objective
response rate, time to next treatment and overall
survival.3
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.
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 one of AstraZeneca's four Growth Platforms
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 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.
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 and Metabolism, and
Respiratory. 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.
Media
Relations
|
|
|
Gonzalo
Viña
|
|
+44 203
749 5916
|
Rob
Skelding
|
Oncology
|
+44 203
749 5821
|
Matt
Kent
|
Oncology
|
+44 203
749 5906
|
Jennifer
Hursit
|
BioPharmaceuticals
|
+44
203 749 5762
|
Christina Malmberg
Hägerstrand
|
Sweden
|
+46 8 552 53 106
|
Michele
Meixell
|
US
|
+1 302
885 2677
|
|
|
|
Investor
Relations
|
|
|
Thomas
Kudsk Larsen
|
|
+44 203
749 5712
|
Henry
Wheeler
|
Oncology
|
+44 203
749 5797
|
Christer
Gruvris
|
BioPharmaceuticals
(CV, Metabolism)
|
+44 203
749 5711
|
Nick
Stone
|
BioPharmaceuticals
(Renal), ESG
|
+44 203
749 5716
|
Josie
Afolabi
|
BioPharmaceuticals
(Respiratory), other medicines
|
+44 203
749 5631
|
Craig
Marks
|
Finance,
fixed income
|
+44
7881 615 764
|
Jennifer
Kretzmann
|
Corporate
access, retail investors
|
+44 203
749 5824
|
US
toll-free
|
|
+1 866
381 72 77
|
References
1. Barf T, et al. Acalabrutinib (ACP-196): A Covalent Bruton
Tyrosine Kinase Inhibitor with a Differentiated Selectivity and In
Vivo Potency Profile. J Pharmacol
Exp Ther. 2017;363 (2)
240-252. Available
online.
Accessed October 2019.
2. American Cancer Society. What Are Myelodysplastic Syndromes?
Available online. Accessed October 2019.
3. ClinicalTrials.gov. Elevate CLL TN: Study of Obinutuzumab +
Chlorambucil, Acalabrutinib (ACP-196) + Obinutuzumab, and
Acalabrutinib in Subjects With Previously Untreated CLL.
NCT02475681. Available online. Accessed October 2019.
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:
06 November
2019
|
By: /s/
Adrian Kemp
|
|
Name:
Adrian Kemp
|
|
Title:
Company Secretary
|