Dr Shah on the Significance of DAYBreak CLL-201 and Bexobrutideg for the CLL Treatment Paradigm

“[DAYBreak CLL-210] is a pivotal phase 2 clinical trial, and hopefully if [the trial is] positive, it will lead to an accelerated approval to make [bexobrutideg] available to patients [who] need it right now… DAYBreak CLL-201 is an opportunity for that patient population to get a drug that can maybe overcome these resistance mutations that may have occurred after exposure to other BTK inhibitors.”

Nirav N. Shah, MD, MSHP an assistant professor of medicine in the Division of Hematology and Oncology at the Medical College of Wisconsin, discussed the ongoing phase 2 DAYBreak CLL-201 trial (NCT07221500) evaluating the BTK degrader bexobrutideg (NX-5948) in patients with relapsed or refractory chronic lymphocytic leukemia (CLL). In addition to discussing the trial and its significance, Shah also explained the appeal of BTK degraders and why they may be pivotal for patients with relapsed or refractory disease.

Shah began by noting that he hopes that the data from trial are positive, which could help support accelerated FDA approval for bexobrutideg in relapsed or refractory CLL. Shah explained how patients enrolled in the trial must have been treated with currently approved options for CLL, including a covalent BTK inhibitor such as acalabrutinb (Calquence), zanubrutinib (Brukinsa), or ibrutinib (Imbruvica), a noncovalent BTK inhibitor like pirtobrutinib (Jaypirca), and a BCL2 inhibitor like venetoclax (Venclexta). Prior treatment with all 3 classes of drugs is mandatory for enrollment, although sequential or combination therapy is allowed.

Shah underscored how patients who have progressed on each of the approved options are often left with limited choices. He emphasized that DAYBreak CLL-201 is a good opportunity for patients to gain access to brexobrutideg, a treatment that may be able to overcome resistance mutations associated with BTK inhibitors. Ultimately, Shah stressed that DAYBreak CLL-201 is actively accruing and an important trial for patients with CLL who have exhausted all available options.