Authored by Ann Liu, PhD
Medically Reviewed by Ed Ratner, MD
The Bottom Line:
This study will investigate whether adding experimental BCL2 inhibitor lisaftoclax to BTKi therapy can improve outcomes for patients with residual CLL.
Who Performed the Research and Where Was it Presented:
Dr. Matthew Davids from Dana-Farber Cancer Institute and colleagues presented the study design at the American Society of Clinical Oncology (ASCO) Annual Meeting in 2026.
Background:
Bruton tyrosine kinase inhibitors (BTKi) such as ibrutinib, acalabrutinib, and zanubrutinib are very effective for treating chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL). With continuous treatment, BTKi produce durable responses in most patients, but they do not produce deep remissions (complete or undetectable measurable residual disease). Eventually, residual CLL cells can mutate and develop resistance to BTKi, which leads to disease progression. Patients with high-risk genetic features are particularly at risk for early disease progression if they have not achieved a complete remission after over a year of BTKi therapy. Adding a BCL2 inhibitor such as venetoclax to a BTKi has been shown to deepen responses and prolong progression-free survival. In this study, researchers are investigating whether adding the experimental BCL2 inhibitor lisaftoclax to BTKi therapy can improve outcomes for patients who still have residual CLL after a year or more of BTKi therapy.
Methods and Participants:
- This is a global phase 3 clinical trial comparing lisaftoclax plus a BTKi with a BTKi alone in patients with residual CLL after BTKi treatment, including sites in 9 U.S. states.
- Eligible patients have been diagnosed with CLL / SLL, have been treated with a BTKi alone for 12 months or more, and have neither achieved a complete remission nor had progressive disease.
- Patients can be included if they have 1) residual disease with high-risk features (deletion 17p, TP53 mutation, unmutated IGHV, complex karyotype) or 2) measurable residual disease with lymph nodes ≥2.5 cm.
- Patients cannot have previously been treated with a BCL2 inhibitor or have Richter transformation.
- Up to 440 patients will be randomly assigned to receive either lisaftoclax plus a BTKi chosen by their physician or to continue their current BTKi therapy.
- Lisaftoclax will be ramped up over five days.
- The primary endpoint is progression-free survival (how long before the disease gets worse).
- Safety and disease assessments will occur regularly.
Conclusions:
This study will compare lisaftoclax plus a BTKi with continuing a BTKi alone in patients who still have residual disease after a year or more of BTKi therapy. This study will further establish how adding a BCL2 inhibitor to BTKi therapy helps patients with residual disease get to deeper remissions, especially for those with high-risk disease.
Lisaftoclax may have a lower risk of tumor lysis syndrome than some other BCL2 inhibitors, allowing for the short ramp-up. If you are interested in participating in this study, more information can be found here: Global Trial in APG2575 for Patients With CLL/SLL.
Links and Resources:
You can read the actual ASCO abstract here: A global multicenter, open-label, randomized, phase 3 registrational study of lisaftoclax (APG-2575) in previously treated chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL / SLL): GLORA trial in progress
Take care of yourself first.
Ann Liu, PhD
