ABBV-101

ABBV-101 is an investigational, orally bioavailable, highly potent and selective Bruton’s tyrosine kinase (BTK) degrader developed for the treatment of relapsed or refractory B-cell malignancies. Unlike traditional BTK inhibitors that only block the catalytic activity of BTK, ABBV-101 induces targeted degradation of the entire BTK protein—including both its catalytic and scaffolding functions—potentially leading to deeper and more durable responses. Preclinical studies have shown that ABBV-101 is effective against both wild-type BTK and multiple therapy-resistant mutant forms (such as C481S), which are associated with resistance to current covalent and reversible BTK inhibitors. The drug has demonstrated high selectivity in kinome profiling, robust anti-tumor activity in various B-cell lymphoma models (including those resistant to other therapies), and enhanced efficacy when combined with BCL2 inhibitors. It is currently being evaluated in a phase 1 clinical trial for adults with relapsed or refractory non-Hodgkin’s lymphomas—including chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma (MCL), follicular lymphoma (FL), marginal zone lymphoma (MZL), Waldenström macroglobulinemia, among others[1][2][4][5][6].