zanubrutinib

BGB-3111 is a potent and highly selective small molecule BTK inhibitor (Bruton’s Tyrosine Kinase), which we are developing as a monotherapy and in combination with other therapies for the treatment of a variety of lymphomas—the most common form of blood cancer. BGB-3111 blocks the signaling that leads to growth inhibition and cell death in malignant B-cells. In preclinical studies, BGB-3111 showed more restricted off-target activities against a panel of kinases, including ITK. Due to the weaker activity on ITK, BGB-3111 was at least 10 times weaker than ibrutinib in inhibiting rituximab-induced ADCC activity. Both in the REC-1 MCL and ABC subtype DLBCL (TMD-8) xenograft models, BGB-3111 induced dose-dependent antitumor effects and demonstrated superior efficacy in comparison with ibrutinib. Toxicity study in rats indicated that BGB-3111 was very well tolerated, and the MTD was not reached when it was dosed up to 250 mg/ kg/day. The first-in-human, open-label phase 1 trial of BGB-3111 is ongoing as a modified 3 + 3 dose-escalation design (40, 80, 160, 320 mg PO QD; 160 mg PO BID) in patients with advanced B cell malignancies. — NCATS