8/5/2023 0 Comments Arq 531![]() ![]() As a reversible inhibitor, ARQ 531 does not require interaction with the C481 residue, a binding site essential for irreversible ibrutinib binding to BTK, thus positioning ARQ 531 as a targeted therapy for patients harboring C481S-mutant BTK who have developed resistance to irreversible BTK inhibitors. Although ibrutinib has demonstrated excellent responses in patients with elevated B-cell receptor signaling, clinical resistance has been observed, and the BTK C481S mutation is emerging as a predominant mechanism of resistance. The only approved BTK inhibitor, ibrutinib, is irreversible and makes a covalent bond with the C481 residue of the targeted protein. A Study of ARQ 531 in Patients With Selected Hematologic Malignancies Latest version (submitted March 10, 2022) on A study version is represented by a row in the table. “We have been working with The Ohio State University in the preclinical development of ARQ 531, and we are looking forward to extending that partnership into clinical testing.”ī-cell malignancies, like chronic lymphocytic leukemia, Waldenstrom’s macroglobulinemia, diffuse large B-cell lymphoma and mantle cell lymphoma are driven by BTK. Brian Schwartz, M.D., head of Research and Development and Chief Medical Officer at ArQule. “There is an emerging body of evidence that is defining the potential clinical need related to BTK resistance, and new molecules are needed to treat patients who have developed resistance,” said Dr. “A clear need is emerging for a BTK inhibitor that addresses resistance.” Both drugs bind noncovalently to the BTK, as opposed to ibrutinib, acalabrutinib, and zanubrutinib, which all bind to the same pocket. Jennifer Woyach, M.D., of the Ohio State University College of Medicine. We also have ARQ 531, which is now with Merck. “Given the emerging data on BTK resistance and the extensive preclinical work the team at The Ohio State University have done with ARQ 531, we are looking forward to moving this drug from the bench to the bedside,” said Dr. The goal would be to establish target engagement and early proof of concept. Upon completion of the phase 1a trial, the company plans to begin a phase Ib trial in a number of expansion cohorts that will include patients with the C481S mutation who are refractory to other therapies. The phase 1a portion will be a dose escalation study open to patients with B-cell malignancies, with the aim of establishing a recommended dose. ARQ 531 is an investigational, orally bioavailable, potent and reversible inhibitor of both wild type and C481S-mutant Bruton’s tyrosine kinase (BTK).ĪrQule plans to initiate a phase Ia/b dose escalation and signal generation trial by Q3 of 2017. ArQule has received clearance from the FDA for the Investigational New Drug (IND) application to conduct a phase I clinical trial with ARQ 531 in patients with B-cell malignancies who are refractory to other therapeutic options. ![]()
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