KN026 + palbociclib + fulvestrant

KN026 + palbociclib + fulvestrant is a combination therapy under investigation for the treatment of HER2-positive and hormone receptor–positive (HR+) advanced or metastatic breast cancer. - **KN026** is a recombinant humanized bispecific monoclonal antibody that targets two distinct domains of the human epidermal growth factor receptor 2 (HER2), specifically binding to epitopes recognized by trastuzumab and pertuzumab. It blocks HER2 signaling, promotes receptor internalization, and mediates antibody-dependent cellular cytotoxicity (ADCC). Developed by Alphamab Oncology, KN026 has shown promising efficacy in clinical trials for HER2-positive breast cancer and gastric/gastroesophageal junction cancers[1][2][4][5][6]. - **Palbociclib** is an oral small molecule inhibitor of cyclin-dependent kinases 4 and 6 (CDK4/6), approved for use in HR+, HER2-negative advanced or metastatic breast cancer. - **Fulvestrant** is a selective estrogen receptor degrader (SERD) that binds to estrogen receptors and accelerates their degradation; it is used in HR+ advanced or metastatic breast cancer. The rationale behind this combination is to simultaneously target the HER2 pathway with KN026 while inhibiting cell cycle progression via CDK4/6 inhibition with palbociclib and blocking estrogen signaling with fulvestrant.