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

Официальное название

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

Обзор

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.

Вмешательства

• Препарат BHB810
  Every 2 weeks IV administration

Первичные конечные точки

• 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) [Срок оценки: 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 [Срок оценки: Cycle 1 Day 1 through 30 days after the last dose, an average of 6 months]
• Overall Response Rate (ORR) [Срок оценки: Screening through End of Treatment, an average of 6 months]

Вторичные конечные точки (12)

• Clinical Benefit Rate (CBR) [Срок оценки: Screening through End of Treatment, an average of 6 months]
• Duration of Response (DOR) [Срок оценки: Screening through End of Treatment or last scan, an average of 6 months]
• Progression Free Survival (PFS) [Срок оценки: Screening through End of Treatment, an average of 6 months]
• Overall Survival (OS) [Срок оценки: Screening through End of Study, an average of 10 months]
• Pharmacokinetics: Area under the concentration-time curve (AUC) [Срок оценки: 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) [Срок оценки: 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) [Срок оценки: 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) [Срок оценки: 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) [Срок оценки: 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) [Срок оценки: 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) [Срок оценки: 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) [Срок оценки: At protocol defined intervals starting at Cycle 1 Day 1 through End of Treatment, an average of 6 months]

Критерии участия

Критерии включения

• 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

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Последовательный дизайн

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 1 центр

• NEXT Virginia — Fairfax

Идентификаторы

NCT: NCT07529808 · BHB810-001

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗