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ASH 2025 | First-in-human Phase I results of a novel BTK inhibitor rocbrutinib in R/R CLL
Jennifer Woyach, MD, The Ohio State University, Columbus, OH, shares findings from a first-in-human Phase I trial (NCT04775745) of the novel BTK inhibitor rocbrutinib in relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL). Dr Woyach highlights that the drug was well-tolerated with encouraging overall response rates. This interview took place at the 67th ASH Annual Meeting and Exposition, held in Orlando, FL.
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Transcript
LP-168, or rocbrutinib, is a novel Bruton’s tyrosine kinase inhibitor. It is a very selective molecule, and in fact, more selective than the other BTK inhibitors that are currently in clinical practice or clinical development. And it has a novel mechanism of action. So if BTK is wild type, the drug can bind covalently, similar to the way ibrutinib, acalabrutinib, and zanubrutinib all bind...
LP-168, or rocbrutinib, is a novel Bruton’s tyrosine kinase inhibitor. It is a very selective molecule, and in fact, more selective than the other BTK inhibitors that are currently in clinical practice or clinical development. And it has a novel mechanism of action. So if BTK is wild type, the drug can bind covalently, similar to the way ibrutinib, acalabrutinib, and zanubrutinib all bind. However, if BTK is mutated at that binding site, like we see in resistance to the covalent BTK inhibitors, it can actually bind non-covalently or reversibly, similar to the way that drugs like pirtobrutinib or nemtabrutinib bind. And importantly, in the laboratory, and I think verified with early clinical data, we see that rocbrutinib is effective in the setting of resistance mutations that show up in patients taking non-covalent BTK inhibitors. So at ASH, we presented updates on the first-in-human Phase I clinical trial of rocbrutinib in patients with CLL. The entire study included other B-cell malignancies, but here we focused on the 42 patients with CLL that were treated. Various dose levels were tested up to 300 milligrams once a day, and no dose-limiting toxicities were identified. The drug was, in fact, very well tolerated due to its selectivity. Only one patient developed atrial fibrillation. There was one patient with a high-grade bleeding side effect associated with a fall. Otherwise, there are the typical things you see in patients with CLL, like low-grade cytopenias, infections, but no clear safety signals with this drug. In terms of efficacy, the overall response rate for patients who received at least 200 milligrams a day of the drug was over 70%. And with a median follow-up of 30 months, the median progression-free survival is 28 months. So it looks very good in this highly refractory patient population. So we look forward to seeing larger clinical trials with rocbrutinib and combination studies, which are all in development.
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