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 B)

Inclusion Criteria:

• histological or cytological diagnosis of ER+ and HER2- advanced/metastatic breastcancer that is not amendable to surgical resection with curative intent (≥1% ER+stained cells on the most recent tumor biopsy).

• prior anticancer therapies: at least 1 and no more than 2 lines of prior therapiesfor advanced/metastatic disease; 1, and only 1, line of any CDK4/6 inhibitor-basedregimen is required (in any setting eg adjuvant, 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 14days 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 and strong/moderate inducers of CYP3A and drugs known to predispose toTorsade de Pointes or QT interval prolongation.

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

• known active infection