A Study of Tucatinib vs. Placebo in Combination With Ado-trastuzumab Emtansine (T-DM1) for Patients With Advanced or Metastatic HER2+ Breast Cancer

Inclusion Criteria:

Histologically confirmed HER2+ breast carcinoma as determined by asponsor-designated central laboratory

History of prior treatment with a taxane and trastuzumab in any setting,separately or in combination

Have progression of unresectable locally advanced/metastatic breast cancerafter last systemic therapy, or be intolerant of last systemic therapy

Measurable or non-measurable disease assessable by RECIST v1.1

ECOG performance status score of 0 or 1

CNS Inclusion - Based on screening contrast brain magnetic resonance imaging (MRI), participants must have at least one of the following: (a) No evidence of brain metastases (b) Untreated brain metastases not needing immediate local therapy (c) Previously treated brain metastases

Exclusion Criteria:

Prior treatment with tucatinib, afatinib, trastuzumab deruxtecan (DS-8201a), orany other investigational anti-HER2, anti-EGFR, or HER2 TKI agent. Priortreatment with lapatinib or neratinib within 12 months of starting studytreatment (except in cases where they were given for ≤21 days and wasdiscontinued for reasons other than disease progression or severe toxicity).Prior treatment with pyrotinib for recurrent of mBC (except in cases wherepyrotinib was given for ≤21 days and was discontinued for reasons other thandisease progression or severe toxicity).

CNS Exclusion - Based on screening contrast brain magnetic resonance imaging (MRI), participants must not have any of the following: