Early Data Demonstrate Clinical Activity of Acalabrutinib in Difficult-to-Treat Chronic Lymphocytic Leukemia
Business WireDecember 5, 2016
WILMINGTON, Del.--(BUSINESS WIRE)--
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), Waldenström 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.