-  Inclusion Criteria:

               -  Histologically confirmed HER2+ breast carcinoma as determined by a
                  sponsor-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 cancer after
                  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), subjects 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

                    1. 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

                    2. Subjects treated with CNS local therapy for newly identified lesions or
                       previously treated and progressing lesions may be eligible to enroll if all
                       of the following criteria are met:

                       (i) Time since SRS is at least 7 days prior to first dose of study
                       treatment, time since WBRT is at least 21 days prior to first dose, or time
                       since surgical resection is at least 28 days.

                       (ii) Other sites of evaluable disease are present

                    3. Relevant records of any CNS treatment must be available to allow for
                       classification of target and non-target lesions

          -  Exclusion Criteria:

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

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

                    1. Any untreated brain lesions >2 cm in size

                    2. Ongoing use of corticosteroids for control of symptoms of brain metastases
                       at a total daily dose of >2 mg of dexamethasone (or equivalent).

                    3. Any brain lesion thought to require immediate local therapy

                    4. Known or concurrent leptomeningeal disease as documented by the investigator

                    5. Poorly controlled generalized or complex partial seizures