ASH 2017 | Phase II results of ACE-LY-004 for acalabrutinib in R/R MCL patients 

The 59^th Annual Meeting & Exposition of the American Society of Hematology (ASH) took place in Atlanta, GA, on 9–12 December 2017. On December 9^th, an oral abstract session was held on “Mantle Cell, Follicular, and Other Indolent B-Cell Lymphoma—Clinical Studies: Mantle Cell Lymphoma, New Therapies”. This session was moderated by Jonathon B Cohen, Emory University - Winship Cancer Institute and Craig A. Portell, University of Virginia.

Abstract #155 was presented during this session, titled “Efficacy and Safety of Acalabrutinib Monotherapy in Patients with Relapsed/Refractory Mantle Cell Lymphoma in the Phase II ACE-LY-004 Study” by Michael Wang, MD, Department of Lymphoma/Myeloma, University of Texas M.D. Anderson Cancer Center, Houston, TX and colleagues. This article is based on data presented at the live session, which may supersede information in the pre-published ASH Abstract.

Study Highlights

• 124 patients with R/R MCL were eligible to be included in the study (median age = 68 years)
• Patients received acalabrutinib (ACP-196) monotherapy, 100 mg twice daily in 28-day cycles until disease progression
• Primary endpoint for the study was overall response rate (ORR) based on the Lugano Classification
• Secondary endpoints included; ORR by an Independent Review Committee (IRC), duration of response (DOR), progression-free survival (PFS), overall survival (OS)
• Results by the IRC at a median follow-up of 15.2 months (0.3–23.7), 56% of patients remained on study therapy:
  • ORR (CR+PR): 81% (95% CI, 73–87)
  • CR: 40% (95% CI, 31–49)
  • PR: 41% (95% CI, 32–50)
  • Median DOR, PFS and OS were not reached
• Results in the Investigator assessed patients:
  • ORR: 80%
  • CR: 40%
  • PR: 40%
• High concordance was observed between investigator- and IRC-assessed ORR and CR (91% and 94%, respectively)
• IRC assessed criteria (exploratory endpoint) was 75% with a CR rate of 30%

Safety

• Most frequent grade 3/4 adverse events (AEs): neutropenia (10%), anemia (9%) and pneumonia (5%)
• One patient died due to worsening aortic stenosis but the event was considered unrelated to the study treatment

The authors noted that acalabrutinib monotherapy was found to have a good safety profile with a high ORR. Acalabrutinib’s pharmacokinetic and selectivity profiles allow twice-daily dosing with minimal off-target effects, while achieving near complete and continuous BTK inhibition over time. Additionally, the median DOR, PFS and OS was not reached, which they suggested showed good duration of treatment response.