MEN1611 + trastuzumab

MEN1611 + trastuzumab is a combination therapy under clinical investigation for the treatment of HER2-positive, PIK3CA-mutated advanced or metastatic breast cancer that has progressed after at least two lines of anti-HER2-based therapy. MEN1611 is an orally bioavailable, selective class I phosphatidylinositol 3-kinase (PI3K) inhibitor with sparing activity against the delta isoform (p110δ), while trastuzumab is a monoclonal antibody targeting the human epidermal growth factor receptor 2 (HER2). The combination aims to overcome resistance mechanisms in tumors driven by PI3K pathway dysregulation and HER2 signaling. Preclinical and early clinical studies have shown that this combination improves antitumor efficacy compared to either agent alone, particularly in models resistant to prior anti-HER2 therapies[1][5][6][7]. The ongoing B-PRECISE-01 phase Ib trial evaluates safety, tolerability, pharmacokinetics/dynamics, and preliminary efficacy of this regimen[4][6].