The goal of this clinical study is to learn more about the study drug sacituzumab govitecan-hziy (SG) given at an alternative dose and schedule, in participants with triple-negative breast cancer (TNBC).

The primary objectives of this study are to assess the safety and tolerability of SG given at alternate dose and schedule, to assess the effect on objective response rate (ORR) and progression-free survival (PFS).

Phase 1 of this study will evaluate the preliminary safety, tolerability, pharmacokinetics (PK), and efficacy of SG. Phase 2 expansion of this study will further evaluate the safety, efficacy, and PK of SG.

Key Inclusion Criteria:

• Individuals assigned male or female at birth, 18 years of age or older, able to understand and give written informed consent.
• Histologically or cytologically locally confirmed TNBC.
• Phase 1: Individuals with unresectable, locally advanced or metastatic TNBC who are refractory to or relapsed after at least one prior standard-of-care chemotherapy regimen or systemic therapy given for locally advanced or metastatic disease.
• Phase 2: Individuals with unresectable, locally advanced or metastatic TNBC who have not received previous systemic therapy for advanced disease.
• Phase 2: Tumors must be PD-L1 negative, defined as tumor PD-L1 combined positive score (CPS) < 10 using the PD-L1 immunohistochemistry (IHC) 22C3 assay. Alternatively, individuals with tumor CPS ≥ 10 will be eligible if they received an anti-PD-(L)1 agent (ie, checkpoint inhibitor) in the adjuvant or neoadjuvant setting or if they cannot be treated with an anti-PD-(L)1 agent. due to a comorbidity.
• Uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) genotype status.

During Phase 1 safety run-in, individuals must be UGT1A1 wild-type.

After Phase 1 safety run-in, individuals with any UGT1A1 genotype may be eligible.

• Measurable disease by computed tomography (CT) or magnetic resonance imaging (MRI) according to RECIST Version 1.1 criteria.
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1.
• Adequate hematologic counts within 2 weeks prior to enrollment.
• Adequate hepatic and renal function.

Key Exclusion Criteria:

• Prior treatment with a topoisomerase 1 inhibitor or antibody-drug conjugate (ADC) containing a topoisomerase inhibitor.
• Prior treatment with a trophoblast cell-surface antigen 2 (Trop-2)-directed ADC.

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