Phase 1/2 Study of BHB810 in Advanced Gastric and GEJ Adenocarcinoma

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.