Authored by Ann Liu, PhD
Medically Reviewed by Brian Koffman, MDCM (retired), MSEd
The Bottom Line:
In a Phase 1 trial, Bexobrutideg produced very good response rates in heavily pretreated patients with CLL / SLL and was generally well-tolerated.
Who Performed the Research and Where Was it Presented:
Dr. Zulfa Omer from the University of Cincinnati and colleagues presented the results at the American Society for Hematology (ASH) Annual Meeting in 2025.
Background:
Bruton tyrosine kinase (BTK) is a key enzyme for the proliferation and survival of chronic lymphocytic leukemia (CLL) / small lymphocytic lymphoma (SLL) cells. Covalent BTK inhibitors (ibrutinib, acalabrutinib, zanubrutinib) bind to a specific site on the BTK enzyme and inhibit its action. However, over time, the BTK protein can mutate and develop resistance to BTK inhibitors. BTK degraders are a new class of drugs that work by destroying the BTK protein. Bexobrutideg is a BTK degrader that is being tested in clinical trials, and researchers now have updated results from a phase 1 clinical trial.
Methods and Participants:
This phase 1 clinical trial tested the BTK degrader bexobrutideg (formerly NX-5948) in patients with relapsed / refractory B-cell cancers, including CLL / SLL. Eligible patients had received 2 or more prior lines of therapy. Patients received doses ranging from 50 mg to 600 mg of bexobrutideg.
Results:
- 230 patients have enrolled in the trial, including 97 with CLL / SLL.
- Patients had received a median of four prior lines of therapy, including: covalent BTKi (98%), non-covalent BTKi (32%), BCL2 inhibitor (74%), BTKi + BCL2i (73%), chemoimmunotherapy (77%), PI3K inhibitor (25%), and CAR-T (6%).
- In patients with CLL / SLL, the overall response rate was 79%.
- Bexobrutideg was generally well-tolerated, with only six patients discontinuing due to side effects.
- The most common side effects were bruising (38%), low neutrophil counts (30%), fatigue (26%), diarrhea (24%), headache (24%), small red spots from broken blood vessels under the skin (24%), and low platelet counts (22%)
Conclusions:
Bexobrutideg produced very good response rates in heavily pretreated patients with CLL / SLL and was generally well-tolerated. BTK degraders may be a useful option for patients who have relapsed after being treated with a BTK inhibitor and a BCL2 inhibitor. This is promising early-stage data, and this study is continuing to recruit patients. Additionally, a phase 2 study has opened for recruitment. If you are interested in participating, more information can be found here:
Phase 1 trial: A Study of NX-5948 in Adults With Relapsed/Refractory B-cell Malignancies
Links and Resources:
Watch the interview on the abstract here:
You can read the actual ASH abstract here: Bexobrutideg (NX-5948), a novel Bruton’s tyrosine kinase (BTK) degrader, demonstrates rapid and durable clinical responses in Relapsed/Refractory chronic lymphocytic leukemia (CLL): New and updated findings from an ongoing Phase 1a/b trial
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