Phase I/II trial findings add to growing body
of data on acalabrutinib clinical profile
AstraZeneca and its hematology Center of Excellence, Acerta
Pharma, today announced preliminary results from the Phase I/II
ACE-CL-001 clinical trial of acalabrutinib in subsets of patients
with two difficult-to-treat forms of chronic lymphocytic leukemia
(CLL), the most common type of leukemia in adults.1 The trial
includes data from individuals with intolerance to ibrutinib and
those with Richter transformation, when CLL transforms into a more
aggressive lymphoma.2 Findings were shared with the medical
community during two oral presentations at the 58th American
Society of Hematology (ASH) Annual Meeting in San Diego,
California.
Acerta Pharma Chief Executive Officer, Flavia Borellini, PhD,
said: “The data at ASH further validate previous clinical trial
findings and continue to demonstrate the potential of acalabrutinib
in the treatment of B-cell malignancies.”
Investigator Jennifer R. Brown, MD, PhD and, Director, Chronic
Lymphocytic Leukemia Center, Dana-Farber Cancer Institute,
said: “The acalabrutinib data in patients in
difficult-to-manage settings support the continued exploration of
acalabrutinib’s potential for the treatment of CLL.”
Acalabrutinib is an investigational, highly selective, potent
Bruton tyrosine kinase (BTK) inhibitor shown to minimize off-target
activity in pre-clinical studies.3,4,5 The Phase I/II findings
presented at ASH are part of an extensive and ongoing clinical
development program for acalabrutinib in B-cell cancers including
CLL, mantle cell lymphoma (MCL), Waldenstr�m macroglobulinemia,
follicular lymphoma and diffuse large B-cell lymphoma.
Results for acalabrutinib in patients intolerant to
ibrutinib
The ibrutinib-intolerant cohort included 33 patients with
relapsed or refractory CLL intolerant to ibrutinib. In this
population with difficult-to-treat disease and limited treatment
options, a 79% overall response rate was achieved with
acalabrutinib.6 The median progression free survival has not yet
been reached, with 81% of responding patients achieving a duration
of response ≥12 months on acalabrutinib treatment,6 which may allow
for continuation of BTK inhibitor therapy.
In this cohort of patients, the most common adverse events
included diarrhea (52% overall; 0% ≥ Grade 3), headache (39%
overall; 0% ≥ Grade 3), cough (24% overall; 0% ≥ Grade 3),
increased weight (24% overall; 0% ≥ Grade 3) and nausea (21%
overall; 0% ≥ Grade 3).6 Serious adverse events occurred in 33% of
patients.6 Thirty six percent of patients had a recurrence of an
adverse event they had experienced during previous treatment with
ibrutinib, most of which were of decreased or the same severity.6
No patients discontinued acalabrutinib due to a recurrent adverse
event.6
Results for acalabrutinib in patients with aggressive
transformation of CLL
In a separate presentation, preliminary data showed the clinical
activity of acalabrutinib monotherapy in a cohort of 29 patients
with Richter transformation, or other transformations—aggressive
B-cell malignancies associated with an aggressive clinical course
and poor prognosis.7 Of the 21 Richter transformation patients
evaluable for efficacy measures, the overall response rate was 38%
and the median progression-free survival was 2.1 months (95% CI,
1.8 to 3.7).7 The median duration of response on acalabrutinib
treatment was 5.2 months (range 0.3 – 6.5+).7
In this cohort of patients, the most common adverse events were
headache (41% overall; 0% ≥ Grade 3), diarrhea (35% overall; 0% ≥
Grade 3), anemia (31% overall; 14% ≥ Grade 3), fatigue (24%
overall; 7% ≥ Grade 3), arthralgia (joint pain) (17% overall; 3% ≥
Grade 3) and back pain (17% overall; 10% ≥ Grade 3).7 Serious
adverse events occurred in 55% of patients. No patients
discontinued acalabrutinib treatment due to adverse events.7
NOTES TO EDITORS
About chronic lymphocytic leukemia and Richter
transformation
Chronic lymphocytic leukemia (CLL) is the most common type of
leukemia in adults and accounts for approximately one in four cases
of leukemia.1,8 The average age at the time of diagnosis is
approximately 71 years of age.8 In CLL, too many blood stem cells
in the bone marrow become abnormal lymphocytes and these abnormal
cells have difficulty fighting infections.9 As the number of
abnormal cells grows there is less room for healthy white blood
cells, red blood cells and platelets.9 This could result in
anaemia, infection and uncontrolled bleeding.9 Approximately 2% to
10% of CLL patients develop Richter transformation, where CLL
transforms into an aggressive lymphoma, most often diffuse large
B-cell lymphoma.10 Prognosis for patients with Richter
transformation is poor, with median overall survival of
approximately eight months.11 B-cell receptor signaling through
Bruton tyrosine kinase (BTK) is one of the essential growth
pathways for CLL.
About acalabrutinib
Acalabrutinib (ACP-196) is an investigational, highly selective,
potent Bruton tyrosine kinase (BTK) inhibitor shown to minimize
off-target activity in pre-clinical studies.3,4,5 Studies of
acalabrutinib have demonstrated clinical activity in monotherapy
with an expected tolerability profile in people with previously
untreated or relapsed or refractory CLL, including those with
del17p.4,12 Acalabrutinib is in ongoing clinical development for
the treatment of a range of B-cell cancers including CLL, MCL,
Waldenstr�m macroglobulinemia, follicular lymphoma and diffuse
large B-cell lymphoma, with both monotherapy and combination
therapy strategies. The acalabrutinib development program also
includes monotherapy and combination studies in solid tumors. In
total, more than 20 acalabrutinib clinical trials with more than
2,000 patients are underway.
About AstraZeneca and Acerta Pharma
Acerta Pharma, a member of the AstraZeneca Group, is a leader in
the field of covalent binding technology and is applying this
technology to create novel selective therapies intended for the
treatment of cancer and autoimmune diseases. The company has
operations in Oss, the Netherlands and multiple US sites. The US
headquarters is in Redwood City, CA. For more information, please
visit www.acerta-pharma.com.
AstraZeneca acquired a majority stake interest in Acerta Pharma
and its cornerstone asset, acalabrutinib, in February 2016. Acerta
Pharma serves as AstraZeneca’s hematology Center of Excellence.
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 New Oncology as one of AstraZeneca’s six
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 hematology.
By harnessing the power of four scientific
platforms–Immuno-Oncology, the genetic drivers of cancer and
resistance, DNA damage response and antibody drug conjugates–and by
championing the development of personalized 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 commercialization of
prescription medicines, primarily for the treatment of diseases in
three main 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-us.com and follow us on Twitter
@AstraZenecaUS.
References
1 Leukemia & Lymphoma Society. Chronic Lymphocytic Leukemia.
https://www.lls.org/leukemia/chronic-lymphocytic-leukemia. Accessed
December 2016.2 National Cancer Institute. NCI Dictionary of Cancer
Terms: Richters Syndrome.
https://www.cancer.gov/publications/dictionaries/cancer-terms?CdrID=489396
Accessed October 2016.3 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):2596.4 Byrd JC,
Harrington B, O'Brien S, Jones JA, Schuh A, Devereux S, et al.
Acalabrutinib (ACP-196) in relapsed chronic lymphocytic leukemia. N
Engl J Med. 2016;374(4):323–332.5 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):2908.6 Global Data on File.
AstraZeneca Pharmaceuticals LP, DoFP Acalabrutinib ASH 2016 Awan F
et al IBR Intolerant 1Dec167 Global Data on File. AstraZeneca
Pharmaceuticals LP, DoFP Acalabrutinib ASH 2016 Hillmen P et al RT
1Dec168 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 2016.9 National Cancer Institute. Chronic
Lymphocytic Leukemia Treatment (PDQ®)–Patient Version.
https://www.cancer.gov/types/leukemia/patient/cll-treatment-pdq
Accessed October 2016.10 Parikh S, et al. How we treat Richter
syndrome. Blood. 2014; 123 (11): 1647-1657.11 Langerbeins P, et al.
Poor efficacy and tolerability of R-CHOP in relapsed/refractory
chronic lymphocytic leukemia and Richter transformation. Am J
Hematol. 2014; 89 (12): E239-E243.12 Byrd JC. Acalabrutinib, a
second-generation bruton tyrosine kinase (Btk) inhibitor, in
previously untreated chronic lymphocytic leukemia (CLL) [abstract].
In: 2016 ASCO Meeting.
http://meetinglibrary.asco.org/content/171180-176. Accessed Nov 28,
2016.
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