abemaciclib + irinotecan + temozolomide

This is a combination of three drugs: **abemaciclib**, a potent and selective small molecule inhibitor of cyclin-dependent kinase 4 and 6 (CDK4/6); **irinotecan**, a topoisomerase I inhibitor; and **temozolomide**, an oral alkylating chemotherapeutic. The combination is being investigated in phase 1 and phase 2 trials for pediatric and young adult patients with relapsed or refractory solid tumors, including rhabdomyosarcoma and Ewing sarcoma or ES-like tumors. The rationale is to pair cell cycle blockade (abemaciclib) with DNA-damaging chemotherapy (irinotecan, temozolomide) to increase tumor inhibition. In a documented case, this combination produced a prolonged complete response in a heavily pretreated patient with alveolar rhabdomyosarcoma and *CDK4* amplification. - **Abemaciclib** acts as a CDK4/6 inhibitor, blocking phosphorylation of the retinoblastoma tumor suppressor, causing G1 arrest and inhibition of cancer cell growth. - **Irinotecan** inhibits DNA topoisomerase I, preventing DNA replication and transcription, leading to cell death. - **Temozolomide** alkylates DNA, resulting in cytotoxicity in replicating cells[2][4][6][7][8].

Other names

abemaciclib + irinotecan + temozolomide