MEN1611 + trastuzumab + fulvestrant

MEN1611 + trastuzumab + fulvestrant is an investigational combination regimen developed for the treatment of HER2-positive, PIK3CA-mutated advanced or metastatic breast cancer that has progressed after at least two lines of anti-HER2 therapy. MEN1611 is an oral, selective phosphoinositide 3-kinase (PI3K) inhibitor that targets the p110α mutant and wild type, β, and γ isoforms, while sparing the δ isoform. Trastuzumab is a monoclonal antibody targeting the human epidermal growth factor receptor 2 (HER2), and fulvestrant is an estrogen receptor antagonist used in hormone receptor-positive breast cancer. The combination aims to overcome resistance to trastuzumab by inhibiting the PI3K pathway in tumors harboring PIK3CA mutations and, for HR-positive patients, blocking estrogen receptor signaling with fulvestrant. Preclinical models and the B-PRECISE-01 phase Ib trial show improved anti-tumor activity and disease control with manageable safety in heavily pretreated patients[1][2][4][5].