Inclusion Criteria:

- Histologically and/or cytologically confirmed adenocarcinoma of the colon or rectum
which is metastatic and/or unresectable

- Able to provide the most recently available formalin-fixed paraffin-embedded (FFPE)
tumor tissue blocks (or freshly sectioned slides) obtained prior to treatment
initiation to a central laboratory

- If archival tissue is not available, a newly-obtained baseline biopsy of an
accessible tumor lesion is required within 35 days prior to start of study
treatment

- HER2+ disease as determined by a tissue based assay performed at a central laboratory.

- Participant has rat sarcoma viral oncogene homolog wild-type (RAS WT) disease as
determined by local or central testing

- Radiographically measurable disease per RECIST v1.1 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 of 0 or 1

- CNS Inclusion - based on contrast brain magnetic resonance imaging, participants may
have any of the following:

- No evidence of brain metastases

- Previously treated brain metastases which are asymptomatic

Exclusion Criteria:

- Prior systemic anticancer therapy for colorectal cancer (CRC) in the metastatic
setting

- May have received chemotherapy for CRC in the adjuvant setting if it was
completed >6 months prior to enrollment

- Radiation therapy within 14 days prior to enrollment (or within 7 days in the setting
of stereotactic radiosurgery)

- Previous treatment with anti-HER2 therapy

- Ongoing Grade 3 or higher neuropathy

- GI perforation within 12 months of enrollment