A Study of Disitamab Vedotin in Adults With HER2 Expressing Advanced Breast Cancer

Inclusion Criteria:

• Histologically or cytologically confirmed diagnosis of locally-advanced,unresectable, or metastatic breast carcinoma.

• Human epidermal growth factor receptor 2 (HER2) and hormone receptor (HR) statusappropriate for enrollment in cohort.

• HER2 status determined by most recent local assessment based on American Society ofClinical Oncology (ASCO) and College of American Pathologists (CAP) guidelines forassessment of HER2 in BC for interpretation of HER2 expression and amplification

• HER2+: immunohistochemistry (IHC) 3+ or IHC 2+/in situ hybridization (ISH)+

• HER2-low: IHC 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) o HR+ disease is determined as either estrogen receptor (ER)and/or progesterone receptor (PgR) positive [ER or PgR ≥1%]) and HR negative diseaseis determined as both ER and PR negative [ER and PgR <1%]) per ASCO/CAP guidelinesin the advanced disease setting. If a patient has had multiple ER/PgR results foradvanced disease, the most recent test result will be used to confirm eligibility.

Prior therapy requirements for Cohort 1 (HER2+, HR+ or HR- participants):

• Received prior trastuzumab, pertuzumab and a taxane if available as local first linestandard of care therapy for advanced disease.

• Prior tucatinib based therapy is allowed.

• Must have progression on or after, or be intolerant to, T-DXd in any line advanceddisease setting.

• No more than 3 prior systemic cytotoxic therapy regimens (including antibody drugconjugates [ADCs]) for Locally Advanced (LA)/metastatic breast cancer (mBC).Participants previously treated with (neo)adjuvant cytotoxic therapy and havedisease relapsed within 6 months of cytotoxic treatment is considered to havereceived 1 line of cytotoxic therapy for LA/mBC.

Prior therapy requirements for Cohort 2 (HR+/HER2-low participants):

• No more than 3 prior systemic cytotoxic therapy regimens (including ADCs) forLA/mBC. Participants previously treated with (neo)adjuvant cytotoxic therapy andhave disease relapsed within 6 months of cytotoxic treatment is considered to havereceived 1 line of cytotoxic therapy for LA/mBC.

• Participants with known germline breast cancer gene (BRCA) mutation must havereceived a poly-ADP ribose polymerase (PARP) inhibitor, where available and notmedically contraindicated.

• Must have progression on or after, or be intolerant to, trastuzumab deruxtecan (T-DXd) in any line advanced disease setting.

• Must have intolerance to endocrine therapy (ET) or ET refractory disease:

• Progressed on ≥2 lines of ET for LA/mBC AND had received a cyclin-dependent kinase (CDK)4/6 inhibitor in the adjuvant or metastatic setting if available as localstandard of care and not contraindicated.

OR

• Progressed on 1 line of ET for LA/mBC AND had a relapse while on adjuvant ET after definitive surgery for primary tumor AND had received a cyclin-dependent kinase (CDK) 4/6 inhibitor in the adjuvant or advanced setting if available as local standard of care and not contraindicated.

Prior therapy requirements for Cohort 3 (HR+/HER2-ultralow or HR-/HER2-low [HER2 low TNBC] participants):

• No more than 4 prior systemic cytotoxic chemotherapy regimens (including ADCs) foradvanced or mBC. Participants previously treated with (neo)adjuvant cytotoxictherapy and have disease relapsed within 6 months of cytotoxic treatment isconsidered to have received 1 line of cytotoxic therapy for LA/mBC.

• Known germline BRCA mutation must have received a PARP-inhibitor if available aslocal standard of care therapy and not medically contraindicated.

• Prior sacituzumab govitecan is allowed.

• Prior T-DXd is allowed.

• Participants with HR negative (TNBC), HER2-low and programmed cell death receptorligand 1 (PD-L1)-positive (combined positive score [CPS] ≥10) tumors must havereceived pembrolizumab (or other PD-L1 inhibitor) with chemotherapy if available aslocal standard of care therapy and not medically contraindicated.

• Participants with HR+/HER2-ultra low tumors must have received at least 1antihormonal therapy in any setting or be ineligible for ET.

• Participants with HR+/HER2-ultra low tumors must have had prior therapy with aCDK4/6 inhibitor in the adjuvant or advanced setting.

Exclusion Criteria:

• Known hypersensitivity to any excipient contained in the drug formulation ofdisitamab vedotin.

• Active central nervous system (CNS) and/or leptomeningeal metastasis.

• Participants with a history of other invasive malignancy within 3 years before theCycle 1 Day 1 (C1D1) of study intervention, or any evidence of residual disease froma previously diagnosed malignancy.

• Prior therapy with ADCs with MMAE payload.

• Participants who have received prior systemic anticancer treatment or radiotherapywithin 2 weeks, or 5 half-lives, whichever is shorter, prior to C1D1 of studyintervention. Note: If the last immediate anticancer treatment contained anantibody-based agent(s), then an interval of 28 days or 5 half-lives (whichever isshorter) of the agent(s) prior to receiving the study intervention treatment isrequired.

• Participants must have recovered from all adverse events due to previoustherapies.