A Study to Learn About Vepdegestrant When Given With PF-07220060 to People With Advanced or Metastatic Breast Cancer.

Inclusion Criteria:

• Histological or cytological diagnosis of breast cancer. At time of enrollment thismust not be amenable to surgical resection with curative intent (≥1% ER+ stainedcells as per local practice on the most recent tumor biopsy HER2- tumor by IHC orin-situ hybridization per ASCO/CAP).

• prior anticancer therapies: Phase 1b: at least 1 line of SOC for A/MBC; Priorfulvestrant allowed; ≤1 prior chemotherapy line (no antibody-drug conjugatespermitted) for A/MBC setting allowed. Phase 2: At least one and maximum 2 lines ofET in A/MBC setting and most recent ET-based regimen for >6 months.

1, and only 1, prior CDK4/6 inhibitor-based regimen required. Up to 1 prior regimenof cytotoxic chemotherapy (no antibody-drug conjugates permitted) in the A/MBCsetting; Prior fulvestrant allowed.

• Participant with only non-measurable lesion (Phase1b) or at least 1 measurablelesion as defined by RECIST v1.1. (Phase2) are eligible.

• ECOG PS = 0 or 1 (Phase1b) ; ≤2 (Phase2)

Exclusion Criteria:

• visceral crisis at risk of life-threatening complications in the short term.

• Any condition precluding an adeguate absorption of study interventions.

• newly diagnosed brain metastases, or symptomatic central nervous system (CNS)metastases, carcinomatous meningitis, or leptomeningeal disease. Participants with ahistory of CNS metastases or cord compression are eligible if they have beendefinitively treated, clinically stable and discontinued anti-seizure medicationsand corticosteroids for at least 28 days prior to enrollment in the of study.

• history of any other tumor malignancies within the past 3 years, except for thefollowing: (1) adequately treated basal or squamous cell carcinoma of the skin; (2)curatively treated in situ carcinoma of the cervix. Inflammatory breast cancer areexcluded

• impaired cardiovascular function or clinically significant cardiovascular diseases.

• concurrent administration of medications, food, or herb supplements that are stronginhibitors/inducers of CYP3A or UGT2B7, moderate inducers of CYP34 (Phase1b only)and drugs known to predispose to Torsade de Pointes or QT interval prolongation.

• renal impairment, not adequate liver function and/or bone marrow function.

• known active infection