In Jordyn Sava’s reporting from Targeted Oncology, readers learn that the U.S. Food and Drug Administration (FDA) granted clearance to a global Phase 3 study. This means that the trial, which is evaluating lisaftoclax for previously treated chronic lymphocytic leukemia (CLL) / small lymphocytic leukemia (SLL), can proceed forward. Participants must have been previously treated with a Bruton’s tyrosine kinase inhibitor.
While numerous treatment advances have improved overall survival rates for CLL and SLL, there are still improvements to be made. Identifying novel and effective therapeutic interventions could further increase survival and improve outcomes.
This study centers around lisaftoclax, an orally bioavailable BH3 mimetic BCL-2-selective inhibitor. In a 2022 paper published in Clinical Cancer Research, the authors explain that:
Development of B-cell lymphoma 2 (BCL-2)-specific inhibitors poses unique challenges in drug design because of BCL-2 homology domain 3 (BH3) shared homology between BCL-2 family members and the shallow surface of their protein-protein interactions. Lisaftoclax selectively binds BCL-2 (Ki < 0.1 nmol/L), disrupts BCL-2:BIM complexes, and compromises mitochondrial outer membrane potential, culminating in BAX/BAK-dependent, caspase-mediated apoptosis.
Lisaftoclax has the potential to overcome some of the challenges in drug development within the space. It selectively binds BCL-2 and culminates in cancer cell “apoptosis,” or cell death. Outside of CLL, lisaftoclax has shown promising antitumor effects in other malignancies like multiple myeloma and Waldenstrom’s macroglobulinemia.
The Upcoming Study
Lisaftoclax has already shown promise in preclinical and clinical studies. 141 participants with relapsed or refractory CLL/SLL enrolled in a Phase 2 clinical study. Cohorts were either given just lisaftoclax, lisaftoclax with acalabrutinib, or with rituximab. 98% of participants receiving the combination of acalabrutinib, and 87% reciving the combination with rituximab, had a response. 65% of people receiving just lisaftoclax had a response to treatment. The drug was also found to be safe and well-tolerated.
The upcoming Phase 3 study is expected to begin before the end of this year.
About Chronic Lymphocytic Leukemia (CLL)
Chronic lymphocytic leukemia is a type of blood cancer that begins in the bone marrow. It is the most common form of leukemia found in adults in Western countries. It affects the white blood cells. Normally, white blood cells protect your body against infection. In CLL, the white blood cells become abnormal. They push healthy blood cells out of the bone marrow. Treatment for CLL is varied. If you have CLL, your treatment options include Campath, Imbruvica, Zydelig, Revlimid, Gazyva, Rituxan, chemotherapy, bone marrow transplants, and more. Please speak with your doctor about the best treatment path for you.
In many cases, symptoms progress as the cancer does; in early stages, many people may show no symptoms. As symptoms appear, they can include:
- Fatigue
- Swollen lymph nodes
- Anemia (low red blood cell count)
- Shortness of breath during exertion
- Unintentional weight loss
- Frequent or recurrent infections
- Fever and night sweats
- Upper left abdominal pain
- An enlarged spleen or liver
