Authored by Ann Liu, PhD
Medically Reviewed by Brian Koffman, MDCM (retired), MSEd
The Bottom Line:
Early-stage clinical trial results show that rocbrutinib appears to be effective in CLL patients with prior exposure to covalent and noncovalent BTKi, and it is generally well-tolerated.
Who Performed the Research and Where Was it Presented:
Dr. Jennifer Woyach from the Ohio State University and colleagues presented the results at the American Society for Hematology (ASH) Annual Meeting in 2025.
Background:
Currently, there are two types of Bruton tyrosine kinase inhibitors (BTKi) approved for the treatment of chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL). Covalent BTKi (ibrutinib, acalabrutinib, zanubrutinib) bind to BTK irreversibly, and noncovalent BTKi (pirtobrutinib) bind to BTK reversibly. Now, there is a new type of BTK inhibitor being tested in clinical trials. Rocbrutinib (formerly LP-168) is a dual BTK inhibitor that can bind to wild-type BTK irreversibly and C481-mutated BTK reversibly.
Methods and Participants:
This treatment is a phase 1 clinical trial of rocbrutinib in patients with relapsed / refractory B-cell cancers. Researchers were looking evaluate the safety of rocbrutinib as well as find the best dose of robrutinib to use in future clinical trials. Patients received doses between 100 and 300 mg.
Results:
- The study included 42 patients with relapsed / refractory CLL who had previously been treated with a BTKi.
- Approximately 45% of patients had been treated with more than one covalent BTKi, 21% had been treated with both a covalent and noncovalent BTKi, and 43% had been treated with a BCL2 inhibitor.
- The overall response rate (how many patients had their cancer shrink) was 78% for patients receiving doses of 200 mg or higher.
- Most side effects were mild, and the most common side effects were diarrhea (41%), cough (36%), headache (36%), joint stiffness (31%), constipation (31%), fatigue (29%), nausea (29%), dizziness (26%), nasal congestion (24%), bruising (21%), muscle spasms (21%), sinus inflammation (21%), and vomiting (21%).
- Only one patient developed atrial fibrillation (abnormal heart rhythm), which is a known side effect of BTKi.
Conclusions:
Early-stage clinical trial results show that rocbrutinib appears to be effective in CLL patients with prior exposure to covalent and noncovalent BTKi, and it is generally well-tolerated. A phase 3 clinical trial comparing rocbrutinib with pirtobrutinib in CLL patients who have already received covalent BTKi therapy is planned. Rocbrutinib could be a potential therapy for patients who have already had multiple lines of therapy, including a covalent and noncovalent BTKi. There is excitement in the research community that its unique dual mechanisms of action in blocking BTK may make it the most promising new therapy for patients running out of options.
Links and Resources:
Watch the interview on the abstract here:
You can read the actual ASH abstract here: Updates of R/R CLL with prior exposure to Bruton’s tyrosine kinase (BTK) inhibitor and/or bcl-2 inhibitor in the Phase 1 trial of LP-168 (Rocbrutinib), a novel COVALENT and non-COVALENT BTK inhibitor
The Expert Interview Series is made possible by support from:
