The primary objective of this study is to compare the progression-free survival (PFS) between sacituzumab govitecan-hziy (SG) versus treatment of physician's choice (TPC) in participants with previously untreated, locally advanced, inoperable or metastatic triple-negative breast cancer whose tumors do not express programmed cell death ligand 1 (PD-L1) or in participants previously treated with anti-programmed cell death (ligand or protein) 1 (Anti-PD-(L)1) Agents in the early setting whose tumors do express PD-L1.

Key Inclusion Criteria:

• Individuals, regardless of race and ethnic group, with previously untreated locally advanced, inoperable or metastatic triple-negative breast cancer (TNBC)

  • Individuals whose tumors are programmed cell death ligand 1 (PD-L1) negative at screening or individuals whose tumors are PD-L1 positive at screening if they have received an anti-PD-(L)1 inhibitor in the (neo) adjuvant setting or if they cannot be treated with a checkpoint inhibitor due to a comorbidity
  • Centrally confirmed TNBC and PD-L1 status on fresh or archival tissue
  • Individuals must have completed treatment for Stage I-III breast cancer, if indicated, and ≥ 6 months must have elapsed (with the exception of endocrine therapy) between completion of treatment with curative intent and first documented local or distant disease recurrence
  • Individuals presenting with de novo metastatic TNBC are eligible

• Measurable disease based on computed tomography (CT) or magnetic resonance imaging (MRI) in accordance with per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1. as evaluated locally

• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

• Demonstrates adequate organ function

• Male individuals and female individuals of childbearing potential who engage in heterosexual intercourse must agree to use protocol-specified method(s) of contraception

• Individuals with human immunodeficiency virus (HIV) must be on antiretroviral therapy (ART) and have a well-controlled HIV infection/disease

Key Exclusion Criteria:

• Positive serum pregnancy test or women who are lactating
• Received systemic anticancer treatment within the previous 6 months or radiation therapy within 2 weeks prior to enrollment
• Have not recovered from adverse events (AEs) due to a previously administered agent at the time study entry
• May not be participating in a study with an investigational agent or investigational device within 4 weeks prior to randomization. Individuals participating in observational studies are eligible
• Previously received topoisomerase 1 inhibitors or antibody drug conjugates containing a topoisomerase inhibitor
• Active second malignancy
• Active serious infection requiring antibiotics
• Positive for HIV-1 or 2 with a history of Kaposi sarcoma and/or Multicentric Castleman Disease
• Active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection

Note: Other protocol defined Inclusion/Exclusion criteria may apply.