zanidatamab + fulvestrant + palbociclib

Zanidatamab + fulvestrant + palbociclib is a triplet combination therapy being investigated for the treatment of hormone receptor-positive (HR+), HER2-positive (HER2+) advanced or metastatic breast cancer. The regimen combines zanidatamab, a biparatopic bispecific antibody that targets two distinct extracellular domains (ECD2 and ECD4) of the HER2 receptor, with fulvestrant, a selective estrogen receptor degrader (SERD), and palbociclib, a CDK4/6 inhibitor. By simultaneously inhibiting the HER2, estrogen receptor, and cell cycle pathways, the combination aims to overcome resistance mechanisms and provide a chemotherapy-free treatment option for heavily pretreated patients. It is currently being evaluated in Phase 2 clinical trials (e.g., NCT04224272) by Zymeworks, Jazz Pharmaceuticals, and Pfizer.