Dr Danilov on the Rationale and Design of DAYBreak CLL-201 Evaluating Bexobrutideg in R/R CLL

“[DAYBreak CLL-201] is a phase 2, open-label study, specifically focused on patients with CLL/SLL…the idea of the study is to better understand the efficacy of bexobrutideg in a BTK inhibitor–pretreated patient population.”

Alexey Danilov, MD, PhD, associate director for Clinical Services, the Marianne and Gerhard Pinkus Professor of Early clinical Therapeutics, medical director of the Early Phase Therapeutics Program for the Systems Clinical Trials Office, co-director of the Toni Stephenson Lymphoma Center, and a professor in the Division of Lymphoma at City of Hope, discussed the design and goal of the ongoing phase 2 DAYBreak CLL-201 trial (NCT07221500), which is evaluating bexobrutideg (NX-5948) in patients with triple-class relapsed or refractory chronic lymphocytic leukemia (CLL).

Following an outline of the trial and its design, Danilov also shared how insights from DAYBreak CLL-201 will help provide context for bexobrutideg in relation to other treatments for relapsed/refractory CLL.

Danilov began by highlighting the core aspects of the trial’s design, which is a global study with over 50 sites, evaluating bexobrutideg in patients with CLL and small lymphocytic leukemia (SLL) with a primary end point of overall response rate. The goal of the study is to provide more insight on the efficacy of bexobrutideg in patient with CLL/SLL who are heavily pretreated, he said.

Danilov then noted the strict enrollment criteria of the trial, specifically noting that patients with CLL must have had prior exposure to a covalent BTK inhibitor, a noncovalent BTK inhibitor, and a BCL2 inhibitor. He underscored how treatment options for this population remain a high unmet need in the field, mentioning that the only treatment to show efficacy in the relapsed or refractory population is lisocabtagene maraleucel (liso-cel; Breyanzi), which received accelerated approval from the FDA for relapsed or refractory CLL in March 2024. However, liso-cel is often accompanied with toxicities that may make it difficult for patients to be eligible for the treatment, he explained. Ultimately, Danilov concluded by emphasizing his excitement for DAYBreak CLL-201 and to potentially address an area of CLL management with a high unmet need.