By Catlin Nalley
CHICAGO—In a phase Ib/II trial, researchers evaluated the activity and tolerability of acalabrutinib, a Bruton tyrosine kinase inhibitor, with the CD20 antibody obinutuzumab in treatment-naive (TN) and relapsed/refractory (R/R) chronic lymphocytic leukemia.
Jennifer Woyach, MD, first author of the study, presented 3-year follow-up results during the 2019 ASCO Annual Meeting (Abstract 7500).
The study enrolled 19 patients with TN CLL and 26 patients with R/R disease. "Acalabrutinib was initially administered at 200 mg daily in the first 15 patients, but after data from the phase I study showed higher BTK occupancy with twice-daily dosing, all patients were treated with 100 mg twice daily going forward," according to Woyach.
Obinutuzumab was started in cycle 2 and administered in standard fashion from cycles 2 to 7, she outlined during her presentation. The primary endpoints, included overall response rate (ORR) and safety. Key primary endpoints were duration of response, progression-free survival, overall survival, minimal residual disease status, and pharmacodynamics.
At a follow-up of about 3 years, 78 percent remain on therapy in remission, Woyach reported. Only two patients have discontinued treatment in the TN group compared to eight in the R/R cohort.
The ORR was 95 percent in the TN group and 92 percent among patients with R/R disease. "As is common with BTK inhibitors, responses have deepened over time," noted Woyach. "[A total of] 31.6 percent of patients TN group have achieved a CR and 7.7 percent in the R/R group.
"In this study, we only performed bone marrow biopsies to confirm CR in patients who had achieved a MRD-negative response in their peripheral blood. So we have potentially underestimated the rate of complete responses by calling some of those MRD-positive potential CRs partial responses."
This combination was generally well-tolerated. Common adverse events (AEs; any grade) included upper respiratory tract infection (71%), increased weight (71%), maculopapular rash (67%), cough (64%), diarrhea (62%), headache (56%), nausea (53%), arthralgia (51%), and dizziness (47%).
Common grade 3/4 AEs were decreased neutrophil count (24%), syncope (11%), decreased platelet count, increased weight, and cellulitis (9% each). There were two (4%) grade 3 bleeding events (hematuria, muscle hemorrhage) and one (2%) grade 3 atrial fibrillation event, according to study authors.
"Treatment with acalabrutinib plus obinutuzumab yielded high response rates that have been durable, irrespective of high-risk disease status," Woyach said. "The combination has been very well-tolerated and most patients have remained on treatment and in remission at 3.5 years.
"Two additional cohorts for this study, one in TN and one in R/R disease, have already been accrued and this includes acalabrutinib with a CD20 antibody with venetoclax. And this particular combination of acalabrutinib plus obinutuzumab is under evaluation as part of a phase III in TN CLL."
Catlin Nalley is a contributing writer.