Key Inclusion Criteria:

• Advanced or metastatic CRC, BTCs, GEA, and PDAC that is histologically or cytologically confirmed
• Disease that has progressed despite prior treatment, for which additional effective therapy is not available, not tolerable, is contraindicated, or the participant refuses standard therapy.
• Platelets ≥ 100,000 /mcL
• Hemoglobin ≥ 9.0 g/dL., no transfusions with RBCs are allowed within 2 weeks prior to first trial drug administration
• ANC ≥ 1500/mcL
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) ≤ 3 x institutional upper limit of normal (ULN) ≤ 5 x ULN if liver metastases present
• Total bilirubin ≤ 1.5 x ULN, unless participant has Gilbert's Syndrome
• Albumin > 2.5 g/dL
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1

Part I

• Fresh biopsy tissue or formalin-fixed paraffin-embedded (FFPE) tumor tissue block or slides available for retrospective assessment of CA242 positivity in a central laboratory.
• Measurable and non-measurable disease

Part II

• Fresh biopsy tissue or FFPE tumor tissue block or slides for assessment of CA242 positivity in a central laboratory prior to administration of first dose of study drug.
• Measurable disease only

Key Exclusion Criteria:

• Participants with a significant pulmonary disease or condition, including:

  • Significant symptomatic chronic obstructive pulmonary disease (COPD), as assessed by the Investigator.
  • History or any current evidence on imaging studies of interstitial lung disease (ILD), pulmonary fibrosis.
  • History of pulmonary inflammatory disease, pneumonitis, acute respiratory distress syndrome (ARDS).
  • History of pneumonia within 3 months prior to the first trial drug administration.

• Participants who have received previous treatment with any CA242 directed ADC or any ADC containing a PBD payload for their current tumor indication.

• Participant may not have received more than 5 prior lines of systemic therapy.

• Received treatment with a strong cytochrome P450 (CYP) 3A4 inhibitor within 7 days or 5 half-lives (whichever is longer) prior to the first trial drug administration

• Central nervous system metastatic disease unless treated prior to first dose of trial drug.

• Active second malignancy or history of another malignancy within the last 2 years with specific exceptions as per protocol

• Active, known or suspected autoimmune disease, or a documented history of autoimmune disease or syndrome requiring systemic steroids or other immunosuppressive medications, such as:

  • Myocarditis, pneumonitis, glomerulonephritis.
  • Autoimmune hepatitis, inflammatory bowel disease (IBD)
  • Sjogren's syndrome
  • Rheumatoid arthritis (RA), systemic lupus erythematosus (SLE)
  • Myositis
  • Myasthenia gravis
  • Guillain-Barré Syndrome
  • Multiple sclerosis
  • Granulomatosis with polyangiitis (Wegner's granulomatosis)
  • Vasculitis