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

Official title

Phase 1/2, Open-Label, Multicenter, Dose Escalation and Expansion Study of BHB810 in Participants With Advanced Gastric and Gastroesophageal Junction Adenocarcinoma

Overview

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.

Interventions

• Drug BHB810
  Every 2 weeks IV administration

Primary outcome measures

• Incidence of adverse events (AEs), serious adverse events (SAEs), and dose limiting toxicities (DLTs) per Common Terminology Criteria for Adverse Events v6.0 (CTCAE v6.0) [Time frame: Cycle 1 Day 1 through 30 days after the last dose, an average of 6 months]
• Incidence of participants who have a dose modification of BHB810 due to toxicity [Time frame: Cycle 1 Day 1 through 30 days after the last dose, an average of 6 months]
• Overall Response Rate (ORR) [Time frame: Screening through End of Treatment, an average of 6 months]

Secondary outcome measures (12)

• Clinical Benefit Rate (CBR) [Time frame: Screening through End of Treatment, an average of 6 months]
• Duration of Response (DOR) [Time frame: Screening through End of Treatment or last scan, an average of 6 months]
• Progression Free Survival (PFS) [Time frame: Screening through End of Treatment, an average of 6 months]
• Overall Survival (OS) [Time frame: Screening through End of Study, an average of 10 months]
• Pharmacokinetics: Area under the concentration-time curve (AUC) [Time frame: At protocol defined intervals starting at Cycle 1 Day 1 through End of Treatment, an average of 6 months]
• Pharmacokinetics: Area under the concentration-time curve from zero to the end of a dosing interval at steady-state (AUC0-tau) [Time frame: At protocol defined intervals starting at Cycle 1 Day 1 through End of Treatment, an average of 6 months]
• Pharmacokinetics: Maximum concentration of BHB810 (Cmax) Phase 1 (Dose Escalation & Backfill Cohorts) Phase 2 (Dose Optimization) [Time frame: At protocol defined intervals starting at Cycle 1 Day 1 through End of Treatment, an average of 6 months]
• Pharmacokinetics: Time to reach maximum drug concentration of BHB810 (Tmax) [Time frame: At protocol defined intervals starting at Cycle 1 Day 1 through End of Treatment, an average of 6 months]
• Pharmacokinetics: Area under the concentration-time curve from zero to infinity (AUC0-inf) [Time frame: At protocol defined intervals starting at Cycle 1 Day 1 through End of Treatment, an average of 6 months]
• Pharmacokinetics: Terminal elimination half-life (t1/2) [Time frame: At protocol defined intervals starting at Cycle 1 Day 1 through End of Treatment, an average of 6 months]
• Pharmacokinetics: Volume of drug distribution during terminal phase (Vz) [Time frame: At protocol defined intervals starting at Cycle 1 Day 1 through End of Treatment, an average of 6 months]
• Pharmacokinetics: Total body clearance of the drug (CL) [Time frame: At protocol defined intervals starting at Cycle 1 Day 1 through End of Treatment, an average of 6 months]

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Sequential

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 1 center

• NEXT Virginia — Fairfax

Identifiers

NCT: NCT07529808 · BHB810-001

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗