Phase 3 rocbrutinib (LP-168) dual covalent/reversible BTK inhibitor vs pirtobrutinib non-covalent BTK inhibitor.

Newave Pharmaceutical is running this Phase 3, randomized, open-label, global multicenter trial in relapsed/refractory CLL/SLL after prior covalent BTK inhibitor therapy, enrolling ~306 adults and randomizing 1:1 to rocbrutinib 200 mg once daily or Eli Lilly’s pirtobrutinib 200 mg once daily in continuous 28-day cycles until progression or intolerance. Rocbrutinib is described as a next-generation BTK inhibitor that irreversibly inhibits wild-type BTK while also reversibly inhibiting BTK C481-mutant disease, aiming to cover common covalent-BTKi resistance biology; pirtobrutinib is a reversible (non-covalent) BTK inhibitor and serves as the active comparator. Stratification includes del(17p)/TP53 mutation, why prior cBTKi was stopped (toxicity vs progression), prior venetoclax-class exposure, and region. The primary endpoint is IRC-assessed PFS using iwCLL 2018 (CLL) and Lugano 2014 (SLL). Commercially, it’s a head-to-head against a post-cBTKi benchmark where current care commonly uses pirtobrutinib, venetoclax-based regimens, and later-line options including clinical trials for double-refractory disease.