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

Prior treatment

• Prior treatment with a CDH17-directed therapy or an ADC with an auristatin (MMAE or MMAF)
• Current treatment with a strong CYP3A4 inhibitor or inducer, Pgp inhibitor, or CYP3A4 sensitive substrate within 2 weeks of first dose of trial intervention

Other illness

• 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
• Known hypersensitivity or allergic reaction to BHB810 or it's excipients
• Known or suspected brain metastases, leptomeningeal disease, or spinal cord compression. Participants with stable, treated brain metastases may be enrolled.
• Any condition that may compromise participant safety, compliance, or interfere with the evaluation of the study drug.

Lab values

• 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

Other

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

• 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