Population and HER2 Status

LA/mBC;

• Cohort 1: HER2-positive (IHC 3+ or IHC2+ and ISH+),
• Cohort 2: HR-positive/HER2-low (IHC 2+ ISH negative or IHC 1+),
• Cohort 3: HR-positive/HER2-ultralow (IHC 0 with membrane staining) or HER2–low, HR negative (triple negative) mBC

Open-Label Study Treatment

Disitamab vedotin monotherapy

Prior therapy requirements

• Cohorts 1 (HER2+, HR+ or HR- participants:
  • No more than 3 prior lines of cytotoxic therapy
  • Progression on, after, or intolerant to T-DXd in any line advanced disease setting
• Cohort 2 (HR+/HER2-low participants):
  • No more than 3 prior lines of cytotoxic therapy
  • Progression on, after, or intolerant to T-DXd in any line advanced disease setting
  • Must have intolerance to endocrine therapy (ET) or ET refractory disease
• Cohorts 3 (HR+/HER2-ultralow or HR-/HER2-low [HER2 low TNBC] participants):
  • No more than 4 prior lines of cytotoxic therapy
  • Prior T-DXd or sacituzumab govitecan is allowed

HER2 and HR status appropriate for enrollment in cohort

• HER+: IHC 3+ or IHC 2+/ISH+
• HER2-low: OHC 1+/ISH-negative or untested or IHC 2+/ISH Negative
• HER2-ultralow: IHC 0 with membrane staining (any staining of the membrane in >0 and ≤10% of cancer cells)

Historically or cytologically confirmed diagnosis of locally advanced, unresectable, or metastatic breast carcinoma

Eastern Cooperative Oncology Group (ECOG) score of 0 or 1

Measurable disease per RECIST v1.1

Known hypersensitivity to any excipient contained in the drug formulation of disitamab vedotin

History of other invasive malignancy within 3 years before study intervention, or any evidence of residual disease from a previously diagnosed malignancy.

Prior therapy with ADCs with MMAE payload

Participants who have received prior systemic anticancer treatment or radiotherapy within 2 weeks to first dose of study treatment

Central nervous system (CNS) and/or leptomeningeal metastasis. Participants with treated CNS metastases are permitted if all of the following are met.

• CNS metastases have been clinically stable for at least 4 weeks without evidence of new or worsening CNS metastasis
• Participant is on a stable or decreasing dose of ≤10 mg/day of prednisone or equivalent
• Participant does not have leptomeningeal metastasis.

Primary outcomes

• Objective response (OR) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) by investigator assessment

Secondary outcomes

• Duration of response (DOR) per RECIST v1.1 by investigator assessment
• Disease control rate (DCR) per RECIST v1.1 by investigator assessment
• Progression free survival (PFS) per RECIST v1.1 by investigator assessment
• Overall survival (OS)
• Estimate of selected Pharmacokinetic (PK) parameter of disitamab vedotin, total antibody, and unconjugated MMAE
• Incidence of anti-drug antibodies (ADAs) against disitamab vedotin
• Safety (type, incidence, severity, seriousness, and relatedness of adverse events [AEs])