Authored by Ann Liu, PhD
Medically Reviewed by Ed Ratner, MD
The Bottom Line:
A phase 3 clinical trial is comparing the efficacy of dual BTKi rocbrutinib with noncovalent BTKi pirtobrutinib in patients with relapsed CLL.
Who Performed the Research and Where Was it Presented:
Dr. Anna Chen from Newave Pharmaceutical and colleagues presented the study design at the American Society of Clinical Oncology (ASCO) Annual Meeting in 2026.
Background:
Covalent Bruton tyrosine kinase inhibitors (BTKi) are a standard first-line therapy for chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL). They bind irreversibly to the BTK protein, and they must be taken continuously. Though they can provide long remissions, many patients eventually relapse, often due to the development of resistance mutations at C481, the site where covalent BTKi bind to BTK. Rocbrutinib is an experimental dual BTKi that can bind both covalently and noncovalently to BTK. It can bind both to wild-type BTK as well as BTK with mutations that commonly cause resistance to covalent BTKi and noncovalent BTKi pirtobrutinib. In this study, researchers are comparing the efficacy of rocbrutinib with pirtobrutinib in patients who have already relapsed on covalent BTKi.
Methods and Participants:
- This is a phase 3 clinical trial comparing rocbrutinib with pirtobrutinib in patients with relapsed / refractory CLL.
- To be eligible, patients must have been previously treated with a covalent BTKi (ibrutinib, acalabrutinib, zanubrutinib).
- Around 300 patients will be randomly assigned to receive either rocbrutinib or pirtobrutinib. The trial is open-label, so patients will know what treatment they are receiving.
- Treatment will be continuous until disease progression, unacceptable toxicity, withdrawal, or other study discontinuation criteria are met.
- The primary endpoint is progression-free survival (how long before the disease gets worse), assessed for up to four years.
- Safety and tolerability will also be assessed.
Conclusions:
In this study, researchers are comparing the efficacy and safety of dual BTKi rocbrutinib with noncovalent BTKi pirtobrutinib in patients with CLL who have already relapsed on covalent BTKi. This is the first study comparing a dual BTKi with a nonvalent BTKi, and it should provide some useful insight into how this new type of BTKi compares to an already approved noncovalent BTKi. If you are interested in participating in this study, more information can be found here: ROCKET-CLL Global Phase 3 Study: Rocbrutinib vs Pirtobrutinib in cBTKi-Pretreated R/R CLL/SLL.
Links and Resources:
You can read the actual ASCO abstract here: ROCKET-CLL: A randomized, open-label, multicenter, phase 3 study of rocbrutinib (LP-168) versus pirtobrutinib in covalent BTK inhibitor (cBTKi) in pretreated relapsed or refractory (R/R) chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL)
Take care of yourself first.
Ann Liu, PhD
