Phase IbII Study of Rocbrutinib Combined With Lacutoclax for Treating Mature B-Cell Cancers

What this Trial Is About

Researchers are evaluating the combination of Rocbrutinib, a fourth-generation Bruton tyrosine kinase inhibitor BTKi, with Lacutoclax, a BCL-2 inhibitor, in patients with mature B-cell malignancies such as Mantle Cell Lymphoma, Diffuse Large B-Cell Lymphoma, Follicular Lymphoma, Waldenstrm Macroglobulinemia, and Chronic Lymphocytic LeukemiaSmall Lymphocytic Lymphoma. This multicenter, open-label, single-arm Phase IbII study aims to investigate the safety, tolerability, pharmacokinetics, and preliminary efficacy of this combination therapy. The Phase Ib portion focuses on dose escalation to find the maximum tolerated dose and recommended dosing regimen, while Phase II further evaluates efficacy and safety. In the Phase Ib dose-escalation study, Rocbrutinib is given at a fixed dose of 150 mg once daily, while Lacutoclax doses will be increased starting at 200 mg daily, then 400 mg daily, in 28-day cycles. Treatment continues until disease progression, unacceptable toxicity, or completion of the planned treatment duration. Phase II participants receive Rocbrutinib alone for 8 to 12 weeks before starting combination treatment, during which Lacutoclax is gradually increased to the target dose and then given continuously. Participants will undergo assessments including monitoring for dose-limiting toxicities, adverse events, and pharmacokinetic measures such as maximum plasma concentration and half-life during and after dosing. Efficacy is assessed by undetectable minimal residual disease rates, overall response rate, progression-free survival, and overall survival over approximately three years. Safety is monitored from the first dose until 28 days after the last dose. The study requires participants to follow treatment and visit schedules, with ongoing evaluations throughout the trial period.

A Study of Rocbrutinib in Combination With Lacutoclax in Patients With B-Cell Malignancies