Phase Ib/IIa Open-label Study, to Evaluate Safety, Tolerability, and Antitumor Activity of HCB101 in Combination With Multiple Agents in Subjects With Advanced Gastric or Gastro-esophageal (GEJ) Adenocarcinoma

NCT07680569 | Not Yet Recruiting Phase 1 DMC

• 1 other identifier: KMUHIRB-F(I)-20250357
• Study Type: interventional
• Target: 40
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is an open-label, dose-escalation and dose-expansion phase Ib/IIa clinical study to evaluate the safety, tolerability, and preliminary efficacy of HCB101 in combination therapies in subjects with gastric or GEJ adenocarcinoma. A total of about 40 subjects will be enrolled in this study. Part-I: Dose-Escalation Phase (Phase Ib) This phase includes Screening, Treatment, and Follow-up Periods: Screening Period: Screening period is up to 28 days (D-28 to D-1) prior to receiving the first dose of HCB101. Treatment Period: This period includes repeat dosing treatment period (42 days per cycle). During the treatment period, subjects from different cohorts will receive HCB101 in combination therapy. Treatment will continue until one of the following occurs: unacceptable adverse event (AE), radiographic or clinically documented disease progression, withdrawal of consent, loss to follow-up, death, or termination of the study, whenever occurs first. Follow-up Period: This period will include Safety and Survival Follow-up Visits. After the last dose in the study, subjects are required to undergo a Safety Follow-up Visit, which will take place 30 (±7) days after the last dose of HCB101, and they will also undergo the Survival Follow-up Visit every 8 weeks (±14 days). The end of treatment (EOT) Visit will coincide with the subject has permanently terminated the study intervention. If the EOT Visit is performed within the time window for the Safety Follow-up Visit, re-examination is not required. Dose Escalation Criteria The study includes four planned dose levels of HCB101(8 mg/kg, 12 mg/kg, 18 mg/kg and 24 mg/kg) The maximum tolerated dose (MTD) will be determined using the standard 3+3 method. To enhance safety during dose escalation, a staggered dosing approach will be applied. The second subject in each dose level should receive treatment staggered by at least 5 days after the first subject has received the 1st dose, provided that no significant safety concerns have been observed.

1. 1.Dose Escalation: The trial begins with the lowest dose, escalating in a stepwise manner. The observation period for dose limiting toxicities (DLT) is from the start of the first dose to day 28 post-dose. The next dose cohort may proceed only after the previous cohort has completed the 28-day DLT observation period and it is confirmed that the subjects are safely tolerated.
2. 2.Initial Cohort: Each dose cohort initially enrols three subjects. If none of these three subjects experience a DLT during the observation period, the next dose cohort will be enrolled.
3. 3.One DLT in a Cohort (1/3): If one out of three subjects experience a DLT, an additional three subjects will be enrolled at that dose level, totally six subjects.

Conditions

GC/GEJC

Keywords

HCB101; GC; GEJC

Outcome Measures

Primary Outcomes (2)

• Number/incidence and percentage of subjects with AEs, SAEs and TEAEs.

  To evaluate the safety and tolerability of HCB101 in combination with zolbetuximab and standard-of-care therapies.

  From signing the ICF at Screening until 30 days after the last administration of the study intervention or Safety Follow-up Visit with an expected observation period of 2 years.

• MTD or RP2D of HCB101 in combination therapy

  To determine the MTD or RP2D of HCB101 in combination therapy

  From 1st dose to Cycle 1 Day 28 (each cycle is 42 days).

Secondary Outcomes (5)

• Objective Response Rate (ORR)

  From first dose to best overall response of CR or PR, with an expected observation period of 2 years.

• Progression-free survival (PFS)

  From first dose to disease progression or death, whichever occurs first, with an expected observation period of 2 years.

• Overall Survival (OS)

  From first dose to death from any cause, with an expected observation period of 2 years.

• Duration of Response (DOR)

  From first documented CR or PR to disease progression or death, with an expected observation period of 2 years.

• Disease Control Rate (DCR)

  From first dose to best overall response of CR, PR, or SD, with an expected observation period of 2 years

Study Arms (2)

HCB101+Zolbetuximab+mFOLFOX6

EXPERIMENTAL

HCB101+Zolbetuximab+mFOLFOX6

Biological: Zolbetuximab; Drug: Oxaliplatin + 5-Fluorouracil/Leucovorin

HCB101+Zolbetuximab+CAPOX

EXPERIMENTAL

HCB101+Zolbetuximab+CAPOX

Biological: Zolbetuximab; Drug: CAPOX (oxaliplatin/capecitabine)

Interventions

Zolbetuximab BIOLOGICAL

First dose (C1D1) 800 mg/m2, followed by 400 mg/m2 every 2 weeks (Q2W) within a 42-day cycle. Those who do not experience disease progression after 12 treatments (4 cycles) of mFOLFOX6 continued with zolbetuximab plus folinic acid and fluorouracil, at investigator discretion. Zolbetuximab treatment will be continued until disease progression, unacceptable toxicity, or other discontinuation criteria are met.

HCB101+Zolbetuximab+CAPOX; HCB101+Zolbetuximab+mFOLFOX6

Oxaliplatin + 5-Fluorouracil/Leucovorin DRUG

Oxaliplatin 85 mg/m2 IV on Day 1, 15 and 29 of a 42-day cycle. Up to 12 treatments (4 cycles). Leucovorin 400 mg/m2 IV on Day 1, 15 and 29 of a 42-day cycle. After 12 treatments (4 cycles), patients are allowed to continue treatment at the investigator's discretion. 5-Fluorouracil (5-FU) 400 mg/m² given as a bolus and 2400 mg/m² continuous IV infusion over 46-48 hours on Day 1, 15 and 29 of a 42-day cycle. After 12 treatments (4 cycles), patients are allowed to continue treatment at the investigator's discretion.

HCB101+Zolbetuximab+mFOLFOX6

CAPOX (oxaliplatin/capecitabine) DRUG

Oxaliplatin 130 mg/m2 IV on Day 1 and 22 of a 42-day cycle. Up to 8 treatments (4 cycles). Capecitabine 1000 mg/m² PO BID on Days 1-14 and Day 22-36 of a 42-day cycle. After 8 treatments (4 cycles), patients are allowed to continue treatment at the investigator discretion.

HCB101+Zolbetuximab+CAPOX

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects are able to understand and willing to provide signed informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol, including study visits and study-related procedures.
• Male and female subjects of ≥18 years of age, inclusive, at the time of signing the informed consent.
• With histologically/cytologically confirmed diagnosis of advanced gastric and gastro-esophageal adenocarcinoma as described below:
• Unresectable locally advanced, or metastatic HER2 (-) gastric or GEJ adenocarcinoma cancer, whose tumors are CLDN 18.2 positive (defined as ≥ 75% of tumor cells demonstrating moderate to strong membranous CLDN 18.2 immunohistochemical staining using an FDA-approved test ( http://www.fda.gov/CompanionDiagnostics).
• Must have at least 1 measurable lesion as defined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
• Must have Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 at Screening.
• Have a life expectancy of ≥12 weeks (according to the Investigator's judgment).
• Have adequate organ function, as indicated by the following laboratory parameters below (had not received a blood transfusion, apheresis infusion, erythropoietin, granulocyte colony-stimulating factor, and other relevant medical support within 14 days before the administration of the first dose of study intervention).
• Absolute neutrophil count ≥1.5 × 109/L
• Platelets ≥100 × 109/L
• Hemoglobin ≥9.0 g/dL
• Total bilirubin ≤1.5 × upper limit of normal (ULN), \<3.0 × ULN if known Gilbert's disease
• Alanine aminotransferase and aspartate aminotransferase ≤3× ULN and ≤5× ULN for subjects with liver metastasis
• Creatinine clearance ≥30 mL/min (using Cockcroft Gault equation)
• Coagulation: International normalized ratio (INR), prothrombin time (PT), and activated partial thromboplastin time (aPTT) ≤1.5× ULN (The INR applies only to subjects who do not receive therapeutic anticoagulation)

You may not qualify if:

• Medical Conditions:
• With a known history of hypersensitivity to any components of the study intervention.
• Subjects who have other malignancies requiring treatment within 2 years before the first dose of study intervention will be excluded, except for radically treated locally curable basal or squamous cell skin cancer and other malignancies that have been treated with no relapse within 2 years.
• Primary tumor in the central nervous system (CNS), or active or untreated CNS metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate, provided they are clinically stable for at least 28 days and have no evidence of new or enlarging brain metastases and no requirements for high-dose corticosteroids 14 days before dosing with study intervention. Subjects on low-dose corticosteroids (\<20 mg prednisone or equivalent per day) may participate.
• Clinically significant cardiovascular condition, including
• History of congestive heart failure (New York Heart Association Class \>2), with only heart failure with preserved ejection fraction (HFpEF) included;
• History of unstable angina within 6 months before the first dose of study intervention;
• New-onset angina or myocardial infarction within 6 months before the first dose of study intervention;
• New-onset of atrial fibrillation, supraventricular arrhythmia, or ventricular arrhythmia within 6 months before the first dose of study intervention and still in unstable condition and requiring treatment or intervention. History of atrial fibrillation, supraventricular arrhythmia, or ventricular arrhythmia will be allowed, provided the condition is stably controlled.
• History or presence of an abnormal ECG that, in the Investigator's opinion, is clinically meaningful (including QT interval corrected for heart rate using Fridericia's correction \[QTcF\] \>470 msec at Screening, pacemaker installation, or previous diagnosis of congenital long QT syndrome).
• Any previous treatment-related toxicities which have not recovered to ≤ Grade 1 as evaluated by National Cancer Institute, Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0 or baseline, except alopecia and anemia (Note: subjects with chronic Grade 2 toxicities which are well managed and stable may be eligible per the discretion of the Investigator, e.g., Grade 2 chemotherapy-induced neuropathy.)
• With known inherited or acquired bleeding disorders or bleeding diathesis.
• Have RBC transfusion dependence defined as requiring more than 2 units of RBC transfusions every 28 days over a period of 3 months before Screening.
• With a previously documented diagnosis of hemolytic anemia or Evans Syndrome in the last 3 months.
• Prior/Concomitant Therapy/Treatment

Sponsors & Collaborators

• Kaohsiung Medical University Chung-Ho Memorial Hospital: lead
• FBD Biologics Limited: collaborator
• China Medical University Hospital: collaborator
• Chi Mei Medical Hospital: collaborator

MeSH Terms

Interventions

zolbetuximab; Oxaliplatin; Fluorouracil; Leucovorin; Capecitabine

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Central Study Contacts

I-Chen Wu

CONTACT

+886-7-3121101; minicawu@gmail.com

Yu-Chi Chang

CONTACT

ashleychang303@outlook.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 3, 2026
• First Posted: July 2, 2026
• Study Start: June 1, 2026
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2027
• Last Updated: July 2, 2026

Record last verified: 2026-06