abemaciclib + fulvestrant + zotatifin

The combination of abemaciclib, fulvestrant, and zotatifin is an investigational regimen for the treatment of estrogen receptor–positive (ER+), human epidermal growth factor receptor 2–negative (HER2-) advanced or metastatic breast cancer. This triplet therapy is being evaluated as a second- or third-line option for patients whose disease has progressed following endocrine therapy and a CDK4/6 inhibitor. Abemaciclib is an oral small molecule inhibitor of cyclin-dependent kinases 4 and 6 (CDK4/6), which blocks cell cycle progression in cancer cells. Fulvestrant is a selective estrogen receptor degrader that binds to and accelerates degradation of the estrogen receptor, inhibiting ER signaling. Zotatifin is a first-in-class small molecule inhibitor targeting eukaryotic initiation factor 4A (eIF4A), suppressing translation of oncogenic proteins including cyclins D/E, CDKs 2/4/6, select receptor tyrosine kinases, and KRAS. Clinical studies have shown promising activity with manageable toxicity in heavily pretreated ER+/HER2– metastatic breast cancer patients[1][3][5]. The FDA granted Fast Track designation to this combination based on its potential to address unmet needs in this patient population[1][5][7].

Brand names

Verzenio (abemaciclib)Faslodex (fulvestrant)

Other names

abemaciclib plus fulvestrant plus zotatifinzotatifin/fulvestrant/abemaciclib combinationZFA triplet