Study of Zelenectide Pevedotin in Participants With Advanced Breast Cancer

Prior treatment

• Prior treatment with any antibody drug conjugate (ADC) containing an Monomethyl Auristatin E (MMAE) (vedotin) payload or other MMAE-based therapy.
• Previously tested HER2-positive (IHC 3+ or ISH+) on prior pathology testing (per ASCO-CAP guidelines).
• Active interstitial lung disease or pneumonitis requiring ongoing treatment with steroids (\>10mg/day of prednisone or equivalent) or other immunosuppressive medications.
• Requirement, while on study, for treatment with strong inhibitors or strong inducers of human cytochrome P450 3A (CYP3A) or inhibitors of P-glycoprotein (P-gp) including herbal- or food-based inhibitors.
• Prior treatment with any systemic anticancer therapy within 28 days or 5 half-lives, whichever is shorter, prior to first dose of study treatment
  • Note: Additional protocol defined Inclusion/Exclusion criteria apply

Other illness

• Known hypersensitivity or allergy to any of the ingredients of any of the study interventions, or to MMAE.
• Uncontrolled diabetes or hypertension.

Other

• Active keratitis or corneal ulcerations.
• Active or untreated central nervous system (CNS) metastases.
• Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently).

• Archival or fresh tumor tissue comprised of TNBC or HR+/HER2-negative invasive breast cancer available for NECTIN4 gene amplification testing.
• Confirmed NECTIN4 gene amplification by an analytically validated clinical trial assay (CTA).
• Measurable disease as defined by RECIST v1.1.
• Life expectancy ≥ 12 weeks.
• Eastern Cooperative Oncology Group Performance Status (ECOG PS) of ≤ 1.
  • Cohort A Specific Inclusion Criteria: Histologically or cytologically confirmed HR+/HER2-negative endocrine resistant/refractory breast cancer according to ASCO-CAP guidelines and received at least 1 and up to 3 prior lines of non-endocrine-based therapy for advanced disease.
  • Cohort B Specific Inclusion Criteria: Histologically or cytologically confirmed TNBC, including ER-low positive breast cancers (1-10% of cells expressing hormonal receptors by IHC), according to ASCO-CAP guidelines and have received at least 1 and up to 3 prior lines of systemic therapy for advanced disease.