A Phase 1/2 Trial of ARV-471 Alone and in Combination With Palbociclib (IBRANCE®) in Patients With ER+/HER2- Locally Advanced or Metastatic Breast Cancer

Inclusion Criteria

• •Part A, Part B, and Part C:
• •Patients at least 18 years of age at the time of signing the informed consent.
• •Patients must have histologically or cytologically confirmed ER+ and HER2- advanced breast cancer for which standard curative therapy is no longer effective or does not exist.
• •Patients must have measurable or non-measurable disease by RECIST criteria (version1.1), with radiologic tumor assessments performed within 28 days of the first dose of therapy.
• •Patients must be willing to undergo a core biopsy of accessible tumor within 4 weeks prior to the initiation of study treatment and a follow-up biopsy on treatment for ER immunohistochemistry (IHC) testing and pharmacodynamics (PD) studies. (Patients without accessible tumor tissue may be eligible after discussion with the Medical Monitor.)
• •Women must be postmenopausal due to surgical or natural menopause.
• •Part A:
• •\- Patients must have received at least 2 prior endocrine regimens in any setting (neoadjuvant, adjuvant or advanced/metastatic) a CDK4/6 inhibitor and up to 3 prior regimens of cytotoxic chemotherapy in the locally advanced or metastatic setting.
• •Part B:
• •Patients must have received at least 1 prior endocrine regimen for a minimum of 6 months in the locally advanced or metastatic setting; if more than 1 prior endocrine regimen has been administered, only one of the regimens must have been administered for a minimum of 6 months in the locally advanced or metastatic setting
• •Patients must have received a CDK4/6 inhibitor
• •Patients must have received up to 1 prior regimen of cytotoxic chemotherapy in the locally advanced or metastatic setting
• •Women must be postmenopausal due to surgical or natural menopause.
• •Part C:
• •Patients must have received at least one prior endocrine regimen.
• •Patients must have received no more than two prior chemotherapy regimens for advanced disease.
• •Women must be postmenopausal due to surgical or natural menopause.
• •Receipt of prior anti-cancer or other investigational therapy within 14 days prior to the first administration of study drug.
• •Radiation therapy within 4 weeks of first dose of study drug or prior irradiation to \>25% of the bone marrow. Palliative radiation for the alleviation of pain due to bone metastasis will be allowed during the study.