Data from two Phase I/II trials presented at
American Society of Hematology Annual Meeting on efficacy and
safety profile of acalabrutinib as monotherapy and combination
treatment1,2
Findings highlight overall response rates
and emerging safety profile of acalabrutinib, a selective Bruton
tyrosine kinase (BTK) inhibitor
AstraZeneca and Acerta Pharma, its haematology research and
development centre of excellence, today presented results from the
Phase Ib/II ACE-CL-003 clinical trial (Abstract #432) and updated
results from the Phase I/II ACE-CL-001 (Abstract #498) clinical
trial that are testing Calquence (acalabrutinib) alone and in
combination for the treatment of chronic lymphocytic leukaemia
(CLL) in multiple treatment settings. The findings were presented
during two oral sessions at the 59th American Society of Hematology
(ASH) Annual Meeting & Exhibition in Atlanta, USA.
Sean Bohen, Executive Vice President, Global Medicines
Development and Chief Medical Officer at AstraZeneca, said: “These
data add to the growing body of evidence that supports the
potential of Calquence in the treatment of chronic lymphocytic
leukaemia, a life-threatening disease that affects tens of
thousands of people around the world. These emerging clinical data
underscore AstraZeneca’s commitment to advancing the science of
blood cancer treatments.”
Jennifer Woyach, MD, Associate Professor of Internal Medicine,
Division of Hematology, The Ohio State University Comprehensive
Cancer Center – Arthur G. James Cancer Hospital and Richard J.
Solove Research Institute, said: “Despite treatment advances for
chronic lymphocytic leukaemia in recent years, the urgent need for
additional treatment options remains. The overall response rates
observed in the acalabrutinib trials and presented at ASH highlight
the potential impact that this investigational treatment could have
on the management of CLL.”
New, early acalabrutinib data from ACE-CL-003
combination therapy trialData on two patient cohorts treated
with acalabrutinib and obinutuzumab from the Phase Ib/II ACE-CL-003
trial were presented. The primary endpoint of overall response rate
was 95% (95% CI: 74,100) for the 19 patients in the treatment-naïve
cohort and 92% (95% CI: 75,99) in the 26 patients with relapsed or
refractory CLL. Additionally, the complete response rate was 16%
for treatment-naïve patients and 8% for previously-treated
patients. At approximately 2 years median study follow-up, the
secondary endpoints of duration of response and median
progression-free survival had not yet been reached in either
patient cohort.
Across both cohorts in the trial, the most common adverse
reactions (≥25%) of any grade were upper respiratory tract
infection (69%), maculopapular rash (64%), increased weight (64%),
diarrhoea (62%), cough (58%), nausea (51%), headache (47%),
infusion-related reaction (42%), contusion (42%), dizziness (42%),
arthralgia (40%), vomiting (40%), constipation (38%), hypertension
(38%), skin lesion (38%), fatigue (36%), peripheral oedema (36%),
decreased appetite (33%), sinusitis (33%), fall (31%), myalgia
(31%), oral pain (31%), dyspepsia (27%) and paraesthesia (27%). One
patient with relapsed or refractory CLL who had a history of atrial
fibrillation experienced intermittent atrial fibrillation (Grade
3), which was not considered treatment related and did not lead to
treatment discontinuation.
Updated acalabrutinib monotherapy efficacy and safety
from ACE-CL-001 trialIn a separate oral session,
investigators presented new longer-term follow-up safety (primary
endpoint) and efficacy (secondary endpoint) data testing
acalabrutinib as a monotherapy in the full-study cohort of 134
patients with relapsed or refractory CLL at median time on study
and follow-up of 24.5 months. These data expand on earlier findings
previously reported in 61 patients at median time on study and
follow-up of 14.3 months.
These latest findings from the trial highlight the overall
response rate and duration of response in this patient population.
With a median time on study and follow-up of 24.5 months, overall
response was 87% (95% CI: 80,92) and the overall response including
partial response with lymphocytosis (increase in number of
lymphocytes in the blood) was 93% (95% CI: 88,97); median duration
of response was not reached. The complete response was 4% (3
patients). The median progression-free survival, a secondary
endpoint in the trial, was not yet reached; however, based on the
Kaplan-Meier estimate, the progression-free survival rate at 18
months was 90% (95% CI: 83,94).
In this trial, the most common adverse reactions (≥20%) of any
grade were diarrhoea (48%), headache (47%), upper respiratory tract
infection (31%), fatigue (28%), nausea (26%), cough (24%),
arthralgia (25%), pyrexia (23%), contusion (23%), weight increased
(21%), petechiae (21%) and constipation (20%). Grade ≥3 adverse
reactions (≥5% of patients) were neutropoenia (12%) and pneumonia
(11%). 22% of patients discontinued treatment.
The Phase I/II CLL clinical trial (ACE-CL-003 and ACE-CL-001)
findings are part of an extensive development programme for
acalabrutinib in a range of blood cancers, which includes three
ongoing Phase III clinical trials (ACE-CL-006, ACE-CL-007 and
ACE-CL-309) in patients with CLL.
– ENDS –
NOTES TO EDITORS
About Calquence (acalabrutinib)Acalabrutinib (previously
known as ACP-196) is a selective inhibitor of Bruton tyrosine
kinase (BTK). Acalabrutinib binds covalently to BTK, thereby
inhibiting its activity, and has demonstrated this with minimal
interactions with other immune cells in pre-clinical
studies.3,4,5,6 In B cells, BTK signalling results in activation of
pathways necessary for B cell proliferation, trafficking,
chemotaxis, and adhesion.3
Calquence was granted accelerated approval by the US Food and
Drug Administration (FDA) in October 2017 for the treatment of
adult patients with mantle cell lymphoma (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. Acalabrutinib is not approved for use
outside of its labelled indication in the US and is not approved in
any other country at this time.
Acalabrutinib is in development for the treatment of multiple
B-cell malignancies and other cancers including CLL, MCL,
Waldenstr�m macroglobulinaemia, follicular lymphoma, diffuse large
B-cell lymphoma, and multiple myeloma. It is also being studied as
a monotherapy and in combination trials for the treatment of solid
tumours. More than 35 clinical trials across 40 countries with more
than 2,500 patients are underway or have completed.7
Acalabrutinib was granted Orphan Drug Designation by the
European Commission in March 2016 and by the US FDA in 2015 for the
treatment of patients with CLL, MCL and WM, and Breakthrough
Therapy Designation in August 2017 by the US FDA for the treatment
of patients with MCL who have received at least one prior
therapy.
About Chronic Lymphocytic LeukaemiaChronic lymphocytic
leukaemia (CLL) is the most common type of leukaemia in adults and
accounts for approximately one in four cases of leukaemia.8,9 The
average age at the time of diagnosis is approximately 71 years of
age.9 In CLL, too many blood stem cells in the bone marrow become
abnormal lymphocytes and these abnormal cells have difficulty
fighting infections.8 As the number of abnormal cells grows there
is less room for healthy white blood cells, red blood cells and
platelets.8 This could result in anaemia, infection and
uncontrolled bleeding.8 B cell receptor signalling through BTK is
one of the essential growth pathways for CLL.
About AstraZeneca in OncologyAstraZeneca has a
deep-rooted heritage in Oncology and offers a quickly-growing
portfolio of new medicines that have the potential to transform
patients’ lives and the Company’s future. With at least six new
medicines aimed to be launched between 2014 and 2020 and a broad
pipeline of small molecules and biologics in development, we are
committed to advance New Oncology as one of AstraZeneca’s five
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 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 Acerta PharmaAcerta Pharma, a member of the
AstraZeneca Group, is creating novel therapies intended for the
treatment of cancer and autoimmune diseases. AstraZeneca acquired a
majority stake interest in Acerta Pharma, which serves as
AstraZeneca’s haematology research and development centre of
excellence. For more information, please visit
www.acerta-pharma.com.
About AstraZenecaAstraZeneca 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 & Metabolic Diseases and Respiratory.
The Company also is selectively active in the areas of
autoimmunity, neuroscience and infection. 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.
Intended audiencesThis press release is issued from
AstraZeneca Corporate Headquarters in Cambridge, UK and is intended
to provide information about our global business. Please be aware
that information relating to the approval status and labels of
approved products may vary from country to country, and a
country-specific press release on this topic may have been issued
in the countries where AstraZeneca conducts business.
___________________________
1 Data on File. REF-23705. AstraZeneca
Pharmaceuticals LP, Wilmington, DE.2 Data on File. REF-23704.
AstraZeneca Pharmaceuticals LP, Wilmington, DE.3 Data on File.
REF-23706. AstraZeneca Pharmaceuticals LP, Wilmington, DE.4
Calquence (acalabrutinib) Prescribing Information. AstraZeneca
Pharmaceuticals LP, Wilmington, DE5 Covey T, Barf T, Gulrajani M,
Krantz F, van Lith B, Bibikova E, et al. Abstract 2596: ACP-196: a
novel covalent Bruton’s tyrosine kinase (Btk) inhibitor with
improved selectivity and in vivo target coverage in chronic
lymphocytic leukemia (CLL) patients. Cancer Res. 2015;75(15
Supplement):2596.6 Harrington BK, Gulrajani M, Covey T, Kaptein A,
Van Lith B, Izumi R, et al. ACP-196 is a second generation
inhibitor of Bruton tyrosine kinase (BTK) with enhanced target
specificity. Blood. 2015;126(23):2908.7 Data on File. REF US-15441.
AstraZeneca Pharmaceuticals LP, Wilmington, DE.8 National Cancer
Institute. Chronic Lymphocytic Leukemia Treatment (PDQ®)–Patient
Version.
https://www.cancer.gov/types/leukemia/patient/cll-treatment-pdq.
Accessed December 2017.9 American Cancer Society. What are the key
statistics for chronic lymphocytic leukemia?
http://www.cancer.org/cancer/leukemia-chroniclymphocyticcll/detailedguide/leukemia-chronic-lymphocytic-key-statistics.
Accessed December 2017.
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AstraZenecaKaren Birmingham, +44 781 852 4012Mike Hayes, +1
301-398-0221Hugues Joublin, +1 301-398-3041