Advanced Gastric Cancer, CDH17-positive Advanced Solid Tumors, Colorectal (Colon or Rectal) Cancer, Gastric Adenocarcinoma, Gastric Cancer, Gastric (Stomach) Cancer, Gastroesophageal Adenocarcinoma, Gastroesophageal Cancer (GC), Gastroesophageal Junction (GEJ) Adenocarcinoma, Gastroesophageal Junction (GEJ) Cancer, Gastrointestinal Adenocarcinoma, Gastrointestinal Cancer Metastatic, Gastrointestinal Cancers, Pancreatic Cancer
Conditions
Keywords
Antibody Drug Conjugate (ADC), Monomethyl Auristatin E (MMAE), CDH17 protein
Brief summary
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
DRUGBHB810
Every 2 weeks IV administration
Sponsors
BigHat Biosciences, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Phase 1 dose escalation with backfill cohorts followed by randomized Phase 2
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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) | Cycle 1 Day 1 through 30 days after the last dose, an average of 6 months | 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. |
| Incidence of participants who have a dose modification of BHB810 due to toxicity | Cycle 1 Day 1 through 30 days after the last dose, an average of 6 months | Investigate the safety and tolerability of BHB810 by assessment of dose modifications due to toxicity Phase 1 (Dose Escalation \& Backfill Cohorts) |
| Overall Response Rate (ORR) | Screening through End of Treatment, an average of 6 months | 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) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Benefit Rate (CBR) | Screening through End of Treatment, an average of 6 months | 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) |
| Duration of Response (DOR) | Screening through End of Treatment or last scan, an average of 6 months | 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) |
| Progression Free Survival (PFS) | Screening through End of Treatment, an average of 6 months | 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) |
| Overall Survival (OS) | Screening through End of Study, an average of 10 months | 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) |
| Pharmacokinetics: Area under the concentration-time curve (AUC) | At protocol defined intervals starting at Cycle 1 Day 1 through End of Treatment, an average of 6 months | To characterize the PK profile of BHB810 in blood samples Phase 1 (Dose Escalation \& Backfill Cohorts) |
| Pharmacokinetics: Area under the concentration-time curve from zero to the end of a dosing interval at steady-state (AUC0-tau) | At protocol defined intervals starting at Cycle 1 Day 1 through End of Treatment, an average of 6 months | To characterize the PK profile of BHB810 in blood samples Phase 1 (Dose Escalation \& Backfill Cohorts) Phase 2 (Dose Optimization) |
| Pharmacokinetics: Maximum concentration of BHB810 (Cmax) Phase 1 (Dose Escalation & Backfill Cohorts) Phase 2 (Dose Optimization) | At protocol defined intervals starting at Cycle 1 Day 1 through End of Treatment, an average of 6 months | To characterize the PK profile of BHB810 in blood samples |
| Pharmacokinetics: Time to reach maximum drug concentration of BHB810 (Tmax) | At protocol defined intervals starting at Cycle 1 Day 1 through End of Treatment, an average of 6 months | To characterize the PK profile of BHB810 in blood samples Phase 1 (Dose Escalation \& Backfill Cohorts) Phase 2 (Dose Optimization) |
| Pharmacokinetics: Area under the concentration-time curve from zero to infinity (AUC0-inf) | At protocol defined intervals starting at Cycle 1 Day 1 through End of Treatment, an average of 6 months | To characterize the PK profile of BHB810 in blood samples Phase 1 (Dose Escalation \& Backfill Cohorts) Phase 2 (Dose Optimization) |
| Pharmacokinetics: Terminal elimination half-life (t1/2) | At protocol defined intervals starting at Cycle 1 Day 1 through End of Treatment, an average of 6 months | To characterize the PK profile of BHB810 in blood samples Phase 1 (Dose Escalation \& Backfill Cohorts) Phase 2 (Dose Optimization) |
| Pharmacokinetics: Volume of drug distribution during terminal phase (Vz) | At protocol defined intervals starting at Cycle 1 Day 1 through End of Treatment, an average of 6 months | To characterize the PK profile of BHB810 in blood samples Phase 1 (Dose Escalation \& Backfill Cohorts) |
| Pharmacokinetics: Total body clearance of the drug (CL) | At protocol defined intervals starting at Cycle 1 Day 1 through End of Treatment, an average of 6 months | To characterize the PK profile of BHB810 in blood samples Phase 1 (Dose Escalation \& Backfill Cohorts) Phase 2 (Dose Optimization) |
| Pharmacokinetics: Area under the concentration-time curve from zero to last measurable concentration sample time (AUC0-last) | At protocol defined intervals starting at Cycle 1 Day 1 through End of Treatment, an average of 6 months | To characterize the PK profile of BHB810 in blood samples Phase 2 (Dose Optimization) |
| Incidence of antidrug antibodies (ADAs) in blood before and after BHB810 administration | At protocol defined intervals starting at Cycle 1 Day 1 through End of Treatment, an average of 6 months | To characterize the ADAs and PK profile of BHB810 in blood samples Phase 1 (Dose Escalation \& Backfill Cohorts) Phase 2 (Dose Optimization) |
Countries
United States
Outcome results
None listed