Clinical Summary: 

• Design/Population: This phase 1a/1b study evaluated bexobrutideg, a BTK degrader, in patients with chronic lymphocytic leukemia or small lymphocytic lymphoma across heavily pretreated, BTK inhibitor-exposed, BTK inhibitor-naïve, and treatment-naïve populations.
• Key Outcomes: Bexobrutideg demonstrated high response rates across cohorts regardless of prior therapy exposure, with durable responses and a favorable safety profile.
• Clinical Relevance: These findings support further development of BTK degradation as a strategy to overcome resistance to BTK inhibitors in this patient population. 

Updated results from a phase 1a/1b study showed that bexobrutideg, a highly selective, oral BTK degrader, continues to demonstrate strong clinical promise among patients with chronic lymphocytic leukemia or small lymphocytic lymphoma.  

These results were presented by Talha Munir, MD, PhD, Leeds Teaching Hospitals NHS Trust, Leeds, United Kingdom, at the European Hematology Association (EHA) Congress in Stockholm, Sweden.

In this first-in-human study, 142 patients with relapsed or refractory, earlier-line, and treatment-naïve chronic lymphocytic leukemia or small lymphocytic lymphoma received bexobrutideg at various dose levels. Efficacy was evaluated in the phase 1a dose-escalation cohort (n = 48) and selected phase 1b expansion cohorts treated at the recommended phase 2 dose of 600 mg, including patients previously exposed to both BTK and BCL2 inhibitors (Cohort 1; n = 42), BTK inhibitor-exposed or BCL2 inhibitor-naïve patients (Cohort 5; n = 19), and BTK inhibitor-naïve patients, including treatment-naïve patients (Cohort 15; n = 20).

Primary objectives included safety and tolerability. Key efficacy end points included objective response rate (ORR) and progression-free survival (PFS).

At safety analysis, bexobrutideg continued to be well tolerated across dose levels and treatment settings. Safety was maintained with most adverse events being grade 1/2 in nature. The most frequently reported treatment-emergent adverse events included purpura or contusion, neutropenia, and petechiae. 

At efficacy analysis, ORR was 83% in phase 1a patients, 83.3% in Cohort 1 patients, 86.7% in Cohort 5 patients, and 84.2% in Cohort 15 patients. Reductions in lymph node size were observed regardless of baseline mutational status or prior therapy exposure. In the phase 1a cohort, median PFS was 22.1 months. 

“In this Ph1a/b trial, bexobrutideg demonstrated a favorable safety profile in pts with CLL/SLL with longer follow-up across doses and prior treatments,” concluded Dr Munir et al. “Bexobrutideg is being evaluated in the Ph2 DAYBreak-201 study and a Ph3 DAYBreak-306 study investigating bexobrutideg vs pirtobrutinib is planned.”

Source:

Munir T, Omer Z, Grosicki S, et al. Updated efficacy and safety data from an ongoing phase 1a/b trial of the BTK degrader bexobrutideg (NX-5948) in patients with CLL across lines of therapy. Presented at EHA Congress. June 11 - June 14, 2026. Stockholm, Sweden. Abstract EHA-1427.