Inclusion Criteria

   - Histologically and/or cytologically documented adenocarcinoma of the colon or rectum
   that is metastatic and/or unresectable

   - Unless contraindicated, participants must have received and failed regimens containing
   the following agents: fluoropyrimidine (e.g., 5-fluorouracil or capecitabine),
   oxaliplatin, irinotecan, an anti-VEGF monoclonal antibody (bevacizumab, ramucirumab,
   or ziv-aflibercept), and an anti-PD-(L)1 therapy (nivolumab or pembrolizumab) if tumor
   has deficient mismatch repair proteins or is MSI-High.

   - Have progression of unresectable or metastatic CRC after the last systemic therapy, or
   be intolerant of last systemic therapy

   - Have RAS wild-type in primary or metastatic tumor tissue, based on expanded RAS
   testing

   - Willing and able to provide the most recently available tissue blocks obtained prior
   to treatment initiation. If archival tissue is not available, then a newly-obtained
   baseline biopsy of an accessible tumor

   - Have confirmed HER2-positive mCRC, as defined by having tumor tissue tested at a
   Clinical Laboratory Improvement Act (CLIA)-certified or International Organization for
   Standardization (ISO)-accredited laboratory, meeting at least one of the following
   criteria:

      - HER2+ overexpression (3+ immunohistochemistry [IHC]) by an FDA-approved or
      Conformité Européene (CE)-marked HER2 ICH test

      - HER2 2+ IHC is eligible if the tumor is amplified by an FDA-approved or CE-marked
      HER2 in situ hybridization assay (FISH or chromogenic in situ hybridization
      [CISH]))

      - HER2 (ERBB2) amplification by CLIA-certified or ISO-accredited next generation
      sequencing (NGS) sequencing assay

   - Have radiographically measurable disease assessable by RECIST 1.1, with at least one
   site of disease that is measurable and that has not been previously irradiated; or, if
   the participant has had previous radiation to the target lesion(s), there must be
   evidence of progression since the radiation

   - Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0, 1, or 2

   - Life expectancy greater than 3 months

   - Have adequate hematological, hepatic, renal, coagulation, and cardiac function

Exclusion Criteria

   - Previous treatment with anti-HER2 targeting therapy

   - Previous treatment with any systemic anticancer therapy, non-central nervous system
   radiation, or experimental agent within 3 weeks of first dose of study treatment

   - Toxicity related to prior cancer therapies that has not resolved to ≤ Grade 1, with
   the following exceptions:

      - Alopecia and neuropathy, which must have resolved to ≤ Grade 2

      - Congestive heart failure (CHF), which must have been ≤ Grade 1 in severity at the
      time of occurrence, and must have resolved completely

      - Anemia, which must have resolved to ≤ Grade 2

      - Decreased ANC, which must have resolved to ≤ Grade 2

   - Have clinically significant cardiopulmonary disease

   - Have known myocardial infarction, unstable angina, cardiac or other vascular stenting,
   angioplasty, or cardiac surgery within 6 months prior to first dose of study treatment

   - Major surgical procedure, open biopsy, or significant traumatic injury ≤28 days prior
   to enrollment (≤56 days for hepatectomy, open thoracotomy, or major neurosurgery) or
   anticipation of need for major surgical procedure during the study

   - Serious, non-healing wound, ulcer, or bone fracture

   - Known to be positive for hepatitis B by surface antigen expression

   - Known to have active hepatitis C infection

      - Exception for participants with a documented sustained virologic response of 12
      weeks

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

   - Subjects who are pregnant, breastfeeding, or planning a pregnancy

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

   - Have used strong CYP2C8 inhibitor within 5 half-lives of the inhibitor, or have used a
   strong CYP2C8 or CYP3A4 inducer within 5 days prior to first dose of study treatment

   - History of another malignancy within 3 years before the first dose of study drug, or
   any evidence of residual disease from a previously diagnosed malignancy.

      - Exceptions are malignancies with a negligible risk of metastasis or death

   - Subjects with known active CNS metastasis

      - Irradiated or resected lesions are permitted, provided the lesions are fully
      treated and inactive, subject is asymptomatic, and no steroids have been
      administered for at least 30 days