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
