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.
