TACTIVE-U: A Study to Learn About the Study Medicine (Vepdegestrant) When Given With Other Medicines in People With Advanced or Metastatic Breast Cancer. (Sub-Study C)

Inclusion Criteria:

• Histological or cytological diagnosis of breast cancer. At time of enrollment thismust not be amendable 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: up to 2 lines of prior therapies for advanced/metastaticdisease; 1 line of any CDK4/6 inhibitor-based regimen is required (in any setting egadjuvant, metastatic)

• at least 1 measurable lesion as defined by RECIST v1.1.

• ECOG PS ≤1.

Exclusion Criteria:

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

• known history of drug-induced pneumonitis or other significant symptomaticdeterioration of lung functions.

• newly diagnosed brain metastases, or symptomatic CNS metastases, carcinomatousmeningitis, or leptomeningeal disease. Participants with a history of CNS metastasesor cord compression are eligible if they have been definitively treated, clinicallystable and discontinued anti-seizure medications and corticosteroids for at least 28days 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

• impaired cardiovascular function or clinically significant cardiovascular diseases

• concurrent administration of medications, food, or herb supplements that are stronginhibitors/inducers of CYP3A, strong CYP2D6 inhibitors and drugs known to predisposeto Torsade de Pointes or QT interval prolongation.

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

• known active infection