KEY Inclusion Criteria:

        Participants must meet all of the following criteria to be eligible for
        randomization/registration into the study:

          1. Adults aged ≥20 years in Japan, Taiwan, and Korea, or those aged ≥18 years in other
             countries, at the time the Informed Consent Forms (ICFs) are signed.

          2. Pathologically-documented, unresectable, recurrent, or metastatic colorectal
             adenocarcinoma. Participants must have v-raf murine sarcoma viral oncogene homologue
             B1 (BRAF) wild-type cancer and rat sarcoma viral oncogenes homologue (RAS) status
             identified in primary or metastatic site.

          3. The following therapies should be included in prior lines of therapy:

               1. Fluoropyrimidine, oxaliplatin, and irinotecan, unless contraindicated

               2. Anti-epidermal growth factor receptor (EGFR) treatment, if RAS wild-type and if
                  clinically indicated

               3. Anti-vascular endothelial growth factor (VEGF) treatment, if clinically indicated

               4. Anti-programmed death ligand 1 (PD-(L)-1) therapy, if the tumor is microsatellite
                  instability (MSI)-high/deficient mismatch repair (dMMR), or tumor mutational
                  burden (TMB)-high, if clinically indicated

          4. Confirmed human epidermal growth factor 2 (HER2)-overexpressing status assessed by
             central laboratory and defined as immunohistochemistry (IHC) 3+ or IHC 2+/ in situ
             hybridization (ISH) +.

          5. Presence of at least one measurable lesion assessed by the Investigator per Response
             Evaluation Criteria In Solid Tumors (RECIST) version 1.1.

          6. Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1.

          7. Has left ventricular ejection fraction (LVEF) ≥50% within 28 days before
             randomization/registration.

        KEY Exclusion Criteria:

        Participants who meet any of the following criteria will be disqualified from entering the
        study:

          1. Medical history of myocardial infarction (MI) within 6 months before
             randomization/registration, symptomatic congestive heart failure (CHF) (New York Heart
             Association Class II to IV). Participants with troponin levels above the upper limit
             of normal (ULN) at Screening (as defined by the manufacturer), and without any
             MI-related symptoms, should have a cardiologic consultation before
             randomization/registration to rule out MI.

          2. Has a corrected QT interval corrected with Fridericia's formula (QTcF) prolongation to
             >470 msec (female participants) or >450 msec (male participants) based on the average
             of the Screening triplicate 12-lead electrocardiograms (ECGs).

          3. Has a history of (non-infectious) interstitial lung disease (ILD)/pneumonitis that
             required steroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis
             cannot be ruled out by imaging at Screening.

          4. Lung-specific intercurrent clinically significant illnesses including, but not limited
             to, any underlying pulmonary disorder (eg, pulmonary emboli within 3 months of the
             randomization/registration, severe asthma, severe chronic obstructive pulmonary
             disease [COPD], restrictive lung disease, pleural effusion, etc.).

          5. Any autoimmune, connective tissue, or inflammatory disorders (eg, rheumatoid
             arthritis, Sjögren syndrome, sarcoidosis, etc.) where there is documented, or a
             suspicion of, pulmonary involvement at the time of Screening.

          6. Prior pneumonectomy.

          7. Has spinal cord compression or clinically active central nervous system metastases,
             defined as untreated and symptomatic, or requiring therapy with corticosteroids or
             anticonvulsants to control associated symptoms. Participants with clinically inactive
             brain metastases may be included in the study. Participants with treated brain
             metastases that are no longer symptomatic and who require no treatment with
             corticosteroids or anticonvulsants may be included in the study if they have recovered
             from the acute toxic effect of radiotherapy. A minimum of 2 weeks must have elapsed
             between the end of whole-brain radiotherapy and randomization/registration.

          8. Participants with leptomeningeal carcinomatosis.

          9. Has known human immunodeficiency virus (HIV) infection.

         10. Active hepatitis B and/or hepatitis C infection, such as those with serologic evidence
             of viral infection within 28 days before study randomization/registration.
             Participants with past or resolved hepatitis B virus (HBV) infection are eligible if
             hepatitis B surface antigen (HBsAg) negative (-) and antibody to hepatitis B core
             antigen (anti-HBc) positive (+).

             Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase
             chain reaction is negative for HCV ribonucleic acid (RNA).

         11. Previous treatment with a DXd-containing antibody-drug conjugate (ADC).