A Study of Vepdegestrant (ARV-471, PF-07850327) Plus Palbociclib Versus Letrozole Plus Palbociclib in Participants With Estrogen Receptor Positive, Human Epidermal Growth Factor Negative Advanced Breast Cancer
The purpose of this study is to understand the safety and effects of the study medicine ARV-471 (PF-07850327) given together with palbociclib in advanced breast cancer. In particular, the study will compare the combination of ARV-471 plus palbociclib to standard of care therapy (letrozole plus palbociclib). Both letrozole and palbociclib are medicines already used for treatment of breast cancer. ARV-471 is a new medicine under study. This study is seeking participants who have breast cancer that: - Have a locally advanced or metastatic disease and cannot be fully cured by surgery or radiation therapy. A metastatic disease is when disease has spread to other parts of the body. - Is sensitive to hormonal therapy such as tamoxifen. This is called estrogen receptor positive disease. - Have not received any prior medicine for advanced disease. Example medications include tamoxifen or letrozole or exemestane. The study will have an open-label SLI (study lead-in) before initiation of Phase 3 trial. During SLI, two dose levels of palbociclib in combination with ARV-471 will be explored in parallel. Assignment to the palbociclib dose is by chance. Half of the participant will receive one dose and the other half another palbociclib dose. The purpose of SLI is to determine the recommended Phase 3 dose of palbociclib to be administered in combination with ARV-471. In the Phase 3, half of the participants will take ARV-471 plus palbociclib while the other half will take letrozole plus palbociclib. In both SLI and Phase 3, participants will take the study medicines by mouth, with food, once a day. Participants will take the study medicines until breast cancer increase in size or side effects become too severe. Side effects refer to unwanted reactions to medications. Participants will visit the study clinic about once every 4 weeks.