NCT07529808 - Phase 1/2 Study of BHB810 in Advanced Gastric and GEJ Adenocarcinoma | Crick

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Outcomes

Primary Outcomes

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)

Investigate the safety and tolerability of BHB810 by evaluation of AEs, SAEs, DLTs, and clinically significant changes safety assessments, like lab tests, vital signs, and other safety assessments Phase 1 (Dose Escalation \& Backfill Cohorts) and Phase 2 (Dose Optimization) DLTs apply to Phase 1 Dose Escalation Cohorts only.

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

Investigate the safety and tolerability of BHB810 by assessment of dose modifications due to toxicity Phase 1 (Dose Escalation \& Backfill Cohorts)

Time frame: Cycle 1 Day 1 through 30 days after the last dose, an average of 6 months

Overall Response Rate (ORR)

Identify the recommended Phase 2 dose (RP2D) by comparing 2 doses of BHB810 by evaluating the ORR of participants according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 Phase 2 (Dose Optimization)

Time frame: Screening through End of Treatment, an average of 6 months

Secondary Outcomes

Clinical Benefit Rate (CBR)

Investigate preliminary antitumor activity of BHB810 as assessed by radiological response per RECIST v1.1 Number of participants who achieve stable disease (SD) for at least 6 months, or PR or CR for any duration Phase 1 (Dose Escalation \& Backfill Cohorts)

Time frame: Screening through End of Treatment, an average of 6 months

Duration of Response (DOR)

Investigate preliminary antitumor activity of BHB810 as assessed by radiological response per RECIST v1.1 Time from PR or CR to disease progression Phase 1 (Dose Escalation \& Backfill Cohorts) Phase 2 (Dose Optimization)

Time frame: Screening through End of Treatment or last scan, an average of 6 months

Progression Free Survival (PFS)

Investigate preliminary antitumor activity of BHB810 as assessed by radiological response per RECIST v1.1 Time from first dose to first documented date of progression per RECIST v1.1 Phase 1 (Dose Escalation \& Backfill Cohorts) Phase 2 (Dose Optimization)

Time frame: Screening through End of Treatment, an average of 6 months

Overall Survival (OS)

Investigate preliminary antitumor activity of BHB810 Time from first dose to death from any cause Phase 1 (Dose Escalation \& Backfill Cohorts) Phase 2 (Dose Optimization)

Time frame: Screening through End of Study, an average of 10 months

Pharmacokinetics: Area under the concentration-time curve (AUC)

To characterize the PK profile of BHB810 in blood samples Phase 1 (Dose Escalation \& Backfill Cohorts)