JS105 + fulvestrant + dalpiciclib

This is a **combination therapy** under investigation for advanced or metastatic breast cancer, particularly in hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, and PIK3CA-mutant populations. The regimen consists of: - **JS105**: a selective inhibitor of phosphoinositide 3-kinase alpha (PI3Kα), developed as an oral small molecule. It is jointly developed by Junshi Biosciences and Risen (Suzhou) Pharma Tech and is designed to target PI3K mutations that drive oncogenic signaling and tumor growth, particularly in breast cancer patients harboring PIK3CA mutations. - **Fulvestrant**: a selective estrogen receptor degrader (SERD) that antagonizes the estrogen receptor and induces its degradation, resulting in antiestrogen effects in hormone receptor-positive cancer. - **Dalpiciclib**: a cyclin-dependent kinase 4/6 (CDK4/6) inhibitor, which blocks cell cycle progression from G1 to S phase, inhibiting proliferation in HR-positive cancer cells. Currently, this combination is being studied in a multi-arm, dose-escalation/expansion phase 1b/2 clinical trial for advanced solid tumors, with a focus on breast cancer with relevant biomarker profiles[1][2][4].