This study is looking at how safe BHB810 is in adults with gastric and gastroesophageal adenocarcinoma (GEJ). The purpose of this study is also to look at: how well the study drug works, how the study drug moves into, through, and out of the body, and how your body reacts to the study drug. Participants will get an IV infusion of BHB810 every 2 weeks while on study treatment.

Inclusion Criteria:

• Participant must be ≥ 18 years or the legal age of consent in the jurisdiction in which the study is taking place at the time of signing the ICF.

• Histologically confirmed advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma that has progressed on, was nonresponsive to, or for which no standard or available curative therapy exists.

  • Participants in Phase 1 Backfill Cohorts & Phase 2 must be CDH17-positive by central testing.
  • Other gastrointestinal (GI) tumor types may be enrolled in Backfill Cohorts and Phase 2.

• At least 1 measurable target lesion at baseline per RECIST 1.1 (Response Evaluation Criteria in Solid Tumors)

• Provision of FFPE archival tumor tissue. Additional fresh biopsies at screening are required in Phase 1 Backfill Cohorts and Phase 2.

• Adequate organ and marrow function as defined in the protocol

Exclusion Criteria:

• Prior cancer treatment as follows, relative to the first planned dose of trial intervention:

  • Chemotherapy or targeted therapy withing 4 weeks or 5-halflives (whichever is shorter)
  • Monoclonal antibody-based therapy (including ADCs) within 4 weeks
  • Immune checkpoint inhibitors within 4 weeks
  • Wide-field radiation therapy (>30% marrow-bearing bones) within 4 weeks or < 2 weeks of focal palliative radiation to nontarget lesions

• Prior treatment with a CDH17-directed therapy or an ADC with an auristatin (MMAE or MMAF)

• Known hypersensitivity or allergic reaction to BHB810 or it's excipients

• Left ventricular ejection fraction <50% or history of congestive heart failure Class III/IV

• QTc interval > 470 msec, history of risk factors for Torsade de Pointes, or taking a medication known to prolong QT/QTc

• Pregnant or breastfeeding females, or if you or your partner are planning to become pregnant

• Known or suspected brain metastases, leptomeningeal disease, or spinal cord compression. Participants with stable, treated brain metastases may be enrolled.

• Current treatment with a strong CYP3A4 inhibitor or inducer, Pgp inhibitor, or CYP3A4 sensitive substrate within 2 weeks of first dose of trial intervention

• Any condition that may compromise participant safety, compliance, or interfere with the evaluation of the study drug.