At the ASH 2018 Annual Meeting, researchers presented preliminary efficacy, safety, and pharmacodynamic results from an ongoing open-label, phase 2 study of acalabrutinib monotherapy in patients with relapsed/refractory (R/R) and high-risk, treatment-naïve chronic lymphocytic leukemia (CLL).
Patients with R/R CLL or previously untreated patients with chromosome del(17p) or mutation in TP53 or NOTCH1 treatment-naïve CLL/small lymphocytic lymphoma with European Cooperative Oncology Group performance status of ≤2 were eligible to participate in the study. Patients who had prior Bruton’s tyrosine kinase (BTK) inhibitor therapy were excluded. Patients were randomized to receive oral acalabrutinib 100 mg twice daily (BID) or 200 mg daily (QD) until progressive disease or unacceptable toxicity. The primary end point was investigator-assessed overall response rate (ORR) and secondary end points included safety and BTK occupancy, a pharmacodynamic end point.
A total of 46 patients were enrolled and treated in the study. Participating patients had a median age of 64 years and 33 (69%) were male. A total of 18 (38%) patients had Rai stage III-IV disease at baseline, 35 (73%) had unmutated IGHV, and 8 (20%) had del(17p). The median time on study for all treated patients was 23.2 months, with 83% remaining on acalabrutinib. Five patients discontinued treatment due to an adverse event (AE).
The investigator-assessed ORR was 89% for evaluable patients, defined by the protocol as patients who had ≥6 months of acalabrutinib. Median progression-free survival and duration of response were not reached. On day 4 of cycle 1, median trough BTK occupancy was significantly higher for the BID group versus the QD group in the peripheral blood (95% vs 87%; P <.001) and in the lymph node (98% vs 90%; P <.001).
With regard to safety, the most common AEs (all grades; >25%) were headache (67% in both the 10-mg BID and 200-mg QD groups) and contusion (63% and 50%, respectively). Grade 3/4 AEs occurred in 35% (17/48) of patients, the most commonly reported of which were infections (15%) and neutropenia (15%). No atrial fibrillation was reported.
In summary, acalabrutinib monotherapy produced high ORR in both R/R and high-risk previously untreated patients, with an acceptable safety profile.
Sun CC, et al. ASH 2018. Abstract 4424.