Acerta (AstraZeneca) Evaluating Acalabrutinib in Ibrutinib-Intolerant R/R Chronic Lymphocytic Leukemia

Jun 3, 2019 | Cancer, Leukemia, Oncology, Precision Medicine Instrumentation Laboratory, Relapsed/Refractory CLL

Richard Simoneaux writing for Oncology Times reported on a phase II study which includes patients with relapsed/refractory CLL who are ibrutinib-intolerant.

The Context

Simoneaux reports that due to adverse events, a number of CLL patients are not able to take advantage of first-in-class Bruton’s tyrosine kinase (BTK) inhibitor ibrutinib.   This reality has led to the development of BTK inhibitors that are designed to have greater selectivity in their targeting of that specific enzyme.

One specific investigational compound is acalabrutinib, an irreversible inhibitor of BTK that forms a covalent linkage to the enzyme. During preclinical research, investigators found that acalabrutinib in fact exhibited more selectivity for BTK inhibition relative to ibrutinib in a panel of several kinases.

The Study

As published in ClincialTrials.gov, the study  titled “A Phase 2 Study of the Efficacy and Safety of ACP-196 in Subjects With Relapsed/Refractory CLL and Intolerant of Ibrutinib” includes patients with relapsed/refractory CLL who are ibrutinib-intolerant.  Sponsored by Acerta Pharma BV, the Phase II, interventional, single group, open-label study targeted 60 participants at 40 research sites in the United States, Europe/UK and Israel.

The study is scheduled to end 2020. It is currently being tested and Oncology Times reported on some highlights of the ASCO presentation.

The Investigator

Kerry Anne Rogers, MD  a hematologist/oncologist at Ohio State University presented at the recent ASCO event in Chicago, IL. Dr. Rogers noted “Although the use of acalabrutinib for CLL is currently off-label, this compound may provide another treatment option to those patients who are ibrutinib-intolerant but were responding to BTK inhibition.”

Results

During the ASCO presentation, it was reported that 60 patients were included with a median age of 70.  Many patients had genomic features associated with high-risk CLL, such as unmutated IGHV-79%, 17p deletion (del17p)-28%, and 11q deletion (del11q)-23% as noted by Oncology Times.

Participants had prior ibrutinib dosing for a median duration of 6 months, with a range of less than 1 to 55 months. A number of common adverse events for ibrutinib were reported among the patient group.

Overall response rate (ORR) for study participants arrived at 77% (95% Cl: 64-87%), with the following responses: CR-2%, PR-70%, and PRL-5%. At the time of reporting for this study, median progression-free survival (PFS) had not been reached. However, the 21-month rate of PFS was 76% (95% Cl: 61-86%).

The median time to follow up reported Oncology Times was 19 months and at that time, 67% of study participants were ongoing receiving acalabrutinib. Discontinuation was primarily due to disease progression (13%) or AEs (10%).  The most common AE observations:

  • Diarrhea 48%
  • Headache 40%
  • Contusion 35%
  • Dizziness 32%

Serious AEs occurring in two or more patients included pneumonia 10%, anemia 3% and syncope 3%. Grade 5 AEs include two cases of pneumonia and one case each of bronchopulmonary aspergillosis and ventricular fibrillation (noteworthy)—it should be noted that they were not deemed to be related to the treatment.

The Sponsor

Based in the Netherlands, Acerta Pharma BV offers drug discovery and development services for oncology and autoimmune diseases. It offers late stage development and early stage development. Founded in 2013, it operates as an subsidiary for global biopharmaceutical owner AstraZeneca.

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