CC-122 + ibrutinib

CC-122 + ibrutinib is an investigational oral combination therapy comprising CC-122 (avadomide), a cereblon E3 ligase modulator (CELMoD), and ibrutinib, a Bruton tyrosine kinase (BTK) inhibitor. CC-122 binds to cereblon in the cullin4 E3 ubiquitin ligase complex, promoting ubiquitination and degradation of transcription factors Aiolos and Ikaros, leading to apoptosis of malignant B cells and immune modulation, including T-cell activation. Ibrutinib covalently binds and inhibits BTK, disrupting B-cell receptor signaling, proliferation, and survival. The combination is being studied primarily in relapsed/refractory B-cell malignancies such as chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and diffuse large B-cell lymphoma (DLBCL), aiming to leverage synergistic immunomodulatory and antineoplastic effects[1][2][3][4][6].