Inclusion Criteria

          -  Have confirmed HER2+ breast cancer, as defined by the current American Society of
             Clinical Oncology - College of American Pathologists (ASCO/CAP) guidelines, previously
             determined at a Clinical Laboratory Improvements Amendments (CLIA)-certified or
             International Organization for Standardization (ISO)-accredited laboratory.

          -  Have received 2 or more prior anti-HER2-based regimens in the metastatic setting

          -  Have progression of unresectable LA/M breast cancer after last systemic therapy (as
             confirmed by investigator), or be intolerant of last systemic therapy

          -  Have measurable disease assessable by RECIST v1.1

          -  Have Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0 or 1

          -  Have a life expectancy of at least 6 months, in the opinion of the investigator

          -  CNS Inclusion - Based on medical history and screening contrast brain magnetic
             resonance imaging (MRI), participants with a history of brain metastases must have one
             of the following:

               -  Untreated brain metastases not needing immediate local therapy. For participants
                  with untreated central nervous system (CNS) lesions >2.0 cm on screening contrast
                  brain MRI, discussion with and approval from the medical monitor is required
                  prior to enrollment

               -  Previously treated brain metastases

                    -  Brain metastases previously treated with local therapy may either be stable
                       since treatment or may have progressed since prior local CNS therapy,
                       provided that there is no clinical indication for immediate re-treatment
                       with local therapy in the opinion of the investigator

                    -  Participants treated with CNS local therapy for newly identified or
                       previously treated progressing lesions found on contrast brain MRI performed
                       during screening for this study may be eligible to enroll if all of the
                       following criteria are met:

                         -  Time since whole brain radiation therapy (WBRT) is ≥14 days prior to
                            first dose of study treatment, time since stereotactic radiosurgery
                            (SRS) is ≥7 days prior to first dose of study treatment, or time since
                            surgical resection is ≥28 days

                         -  Other sites of measurable disease by RECIST v1.1 are present

                    -  Relevant records of any CNS treatment must be available

        Exclusion Criteria

          -  Have previously been treated with:

               -  Lapatinib or neratinib within 12 months of starting study treatment (except in
                  cases where lapatinib or neratinib was given for ≤21 days and was discontinued
                  for reasons other than disease progression or severe toxicity)

               -  Tucatinib or enrolled on a tucatinib clinical trial

               -  Any investigational HER2/epidermal growth factor receptor (EGFR) or HER2 tyrosine
                  kinase inhibitor (TKI) (eg, afatinib) at any time previously

               -  Trastuzumab deruxtecan or another antibody-drug conjugate (ADC) consisting of an
                  exatecan derivative

          -  Have received treatment with:

               -  Any systemic anti-cancer therapy (including hormonal therapy) or experimental
                  agent ≤21 days of first dose of study treatment or are currently participating in
                  another interventional clinical trial. An exception for the washout of hormonal
                  therapies is gonadotropin releasing hormone (GnRH) agonists used for ovarian
                  suppression in premenopausal women, which are permitted concomitant medications

               -  Treatment with non-CNS radiation ≤7 days prior to first dose of study treatment

               -  Major surgery <28 days of first dose of study treatment

          -  Have clinically significant cardiopulmonary disease (such as history of iterstitial
             lung disease (ILD)/pneumonitis that required systemic corticosteroids, or have current
             ILD/pneumonitis, or where suspected ILD /pneumonitis cannot be ruled out be imaging at
             screening)

          -  Have known myocardial infarction or unstable angina within 6 months prior to first
             dose of study treatment

          -  Known to be positive for hepatitis B by surface antigen expression. Known to be
             positive for hepatitis C infection. Participants who have been treated for hepatitis C
             infection are permitted if they have documented sustained virologic response of 12
             weeks

          -  Presence of known chronic liver disease

          -  Known to be positive for human immunodeficiency virus (HIV)

          -  Active or uncontrolled clinically serious infection

          -  Are pregnant, breastfeeding, or planning a pregnancy

          -  Have inability to swallow pills or significant gastrointestinal disease which would
             preclude the adequate oral absorption of medications