Authored by Ann Liu, PhD
Medically Reviewed by Ed Ratner, MD
The Bottom Line:
In a phase 1 study, BTK degrader bexobrutideg produced high response rates in patients with relapsed CLL who had received a range of different prior therapies.
Who Performed the Research and Where Was it Presented:
Dr. Talha Munir from St. James Hospital in Leeds, UK and colleagues presented the results at the European Hematology Association (EHA) Annual Meeting in 2026.
Background:
Bruton tyrosine kinase (BTK) is an enzyme that helps promote prolonged lifespan and excess multiplication of lymphocytes in chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL). BTK inhibitors (BTKi) are very effective for treating CLL / SLL. However, over time, patients can develop resistance mutations that prevent the drug from binding to BTK. The BTK degraders are a new class of drugs that get around this problem by destroying the entire BTK protein. Bexobrutideg is one of several experimental BTK degraders in development for treating CLL / SLL. We have previously covered initial results of a phase 1 clinical trial of bexobrutideg for relapsed CLL, and now researchers have reported their updated results.
Methods and Participants:
This phase 1 clinical trial is testing the safety of bexobrutideg (formerly NX-5948) in patients with B-cell cancers. This analysis specifically looked at patients with relapsed / refractory CLL / SLL. This study also had several different cohorts:
- Phase 1a dose-escalation cohort – patients received different dose levels ranging from 50 to 600 mg
- Phase 1b dose-expansion – patients received the recommended phase 2 dose level of 600 mg. There are 17 different phase 1b cohorts, but this report focused on three of them.
- Cohort 1 – BTKi and BCL2 inhibitor (BCL2i e.g. venetoclax) exposed
- Cohort 5 – BTKi-exposed, BCL2i-naïve
- Cohort 15 – BTKi-naïve, including treatment-naïve
Results:
- At the time of analysis, 142 patients with CLL / SLL had enrolled in the trial.
- Safety has been reported previously, and no new side effects of concern have emerged since the last report. Common side effects include bruising, low neutrophil counts, and small red spots from broken blood vessels under the skin.
- Overall response rates were high across all cohorts (see table below).
| Cohort | Overall Response Rate | Median Follow-up |
| Phase 1a, (n=48) | 83% | 22 months |
| Phase 1b Cohort 1, (n=42) BTKi +, BCL2i + | 83% | 13 months |
| Phase 1b Cohort 5, (n=19) BTKi +, BCL2i – | 87% | 5 months |
| Phase 1b Cohort 15, (n=20) BTKi – | 84% | 5 months |
- Lymph node size decreased across all cohorts irrespective of prior treatments or baseline mutational status (BTK, PLCG2, TP53, SF3B1, ATM, NOTCH1).
- In the phase 1a cohort, median progression-free survival was 22 months.
Conclusions:
BTK degrader bexobrutideg produced high response rates in patients with relapsed CLL who had received a range of different prior therapies. Patients also seemed to respond irrespective of baseline mutational status. The response rates reported are comparable to those for a similar population receiving pirtobruitinib in the BRUIN CLL-314 phase 3 trial. It is still early in the study, so we will have to wait to learn more about the durability of the responses, but thus far the data are encouraging. BTK degraders may be especially useful for patients who have already been treated with a BTK inhibitor and a BCL2 inhibitor. A phase 2 and a phase 3 study are currently open for recruitment. If you are interested in participating, more information can be found here:
Phase 3 trial: Study of NX-5948 Versus Pirtobrutinib in R/R CLL/SLL
Links and Resources:
You can read the actual EHA abstract here: 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
Take care of yourself first. Ann Liu, PhD
