Authored by Ann Liu, PhD
Medically Reviewed by Ed Ratner, MD
The Bottom Line:
BTK degrader BGB-16673 reduced tumor burden in 85% of patients from a high-risk, hard-to-treat group with relapsed / refractory CLL.
Who Performed the Research and Where Was it Presented:
Dr. Stephan Stilgenbauer from Ulm University and colleagues presented the results at the European Hematology Association (EHA) Annual Meeting in 2026.
Background:
Bruton tyrosine kinase (BTK) inhibitors have been successfully used to treat chronic lymphocytic leukemia (CLL) / small lymphocytic lymphoma (SLL) for many years. However, patients can develop resistance mutations that prevent BTK inhibitors from binding, leading to relapse. BTK degraders are a new, experimental class of drugs that completely degrade the BTK protein rather than inhibiting it. BGB-16673 (now named catadegbrutinib) is an experimental BTK degrader in development for the treatment of CLL / SLL. Here, researchers provided an update on the results of a phase 1 clinical trial of BGB-16673 in patients with relapsed / refractory CLL.
Methods and Participants:
The CaDAnCe-101 study is a phase 1/2 clinical trial looking at the safety and preliminary efficacy of BGB-16673 in patients with B-cell cancers. This analysis specifically looked at patients with relapsed / refractory CLL / SLL who had two or more prior therapies.
Results:
- A total of 67 patients with relapsed / refractory CLL / SLL were treated with BGB-16673 orally each day, at various doses.
- These patients tended to be at higher risk.
- Half of the patients were older than 70 years of age.
- 77% had unmutated IGHV.
- 66% had deletion 17p / TP53 mutation.
- Patients had received a median of four prior lines of therapy.
- 94% had been treated with a covalent BTK inhibitor.
- 82% had been treated with a BCL2 inhibitor.
- 21% had been treated with a noncovalent BTK inhibitor.
- 64% had failed both a covalent BTK inhibitor and a BCL2 inhibitor.
- Median follow-up was two years, with about half still on treatment as of the end of 2025.
- Almost all patients experienced a side effect during the study, and the most common side effects were fatigue (37%), bruising (33%), diarrhea (30%), and low neutrophil count (30%).
- Five patients died related to treatment, all with infection, with one also due to disease progression.
- The most common severe side effects were infections (35%) and low neutrophil counts (25%).
- Side effects led to dose reduction in 13% of patients and treatment discontinuation in 18% of patients.
- The overall response rate (i.e., number with improvement in blood counts other than lymphocytes, feeling better, and shrinkage of lymph nodes) was 85%, and over 75% of patients had such a response across all genetically high-riskgroups.
- 80% of these patients, who had previously failed all standard treatment options, were still alive two years after starting treatment with BGB-16673.
- The 18-month progression-free survival rate was 65%.
Conclusions:
As a next step, researchers are conducting a phase 3 clinical trial to compare the efficacy of BGB-16673 versus noncovalent BTK inhibitor pirtobrutinib for relapsed / refractory CLL, with sites in 24 US states and around the world. Another phase 2 clinical trial is evaluating the efficacy of the combination of BGB-16673 plus sonrotoclax (an experimental BCL2 inhibitor) for treatment-naïve CLL. BTK degraders are a promising new option in development for the treatment of CLL / SLL, adding hope for those who fail other treatments.
Links and Resources:
Watch the interview here:
You can read the actual EHA abstract here: BGB-16673, A Bruton Tyrosine Kinase (BTK) Degrader, In Patients With Relapsed/Refractory (R/R) Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL / SLL): A Phase 1 Cadence-101 Study Update
Take care of yourself first.
Ann Liu, PhD
