GFH009 + zanubrutinib

GFH009 + zanubrutinib is an investigational combination therapy composed of GFH009, a small molecule CDK9 inhibitor, and zanubrutinib, an approved small molecule inhibitor of Bruton's tyrosine kinase (BTK, branded as Brukinsa). GFH009 is being developed by GenFleet Therapeutics and acts by inhibiting cyclin-dependent kinase 9 (CDK9), leading to the downregulation of anti-apoptotic proteins such as MYC and MCL1, promoting cancer cell apoptosis. Zanubrutinib, developed by BeiGene, is a second-generation, highly selective, irreversible BTK inhibitor that blocks BTK signaling critical for malignant B-cell proliferation and survival. The combination is being evaluated in phase Ib/II clinical trials for relapsed/refractory diffuse large B-cell lymphoma (DLBCL), where it has shown promising synergistic efficacy, with an overall response rate notably higher than zanubrutinib monotherapy.