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

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. 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. 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. 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.

1\) Two or More DLTs (2+/6): If one or more of the additional three subjects experience a DLT (resulting in two or more DLTs at this dose level), dose escalation will stop, and the previous dose will be designated as the MTD, or the SRC may decide to use an intermediate dose for further investigation.

2\) No Additional DLTs (1/6): If none of the additional three subjects experience a DLT (resulting in one DLT out of six), the trial will proceed to the next higher dose level.

4\) Two or More DLTs in a Cohort (≥2/3): If two or more out of three subjects experience a DLT, dose escalation will conclude, and the previous dose will be considered the MTD, or the SRC may determine whether to use an intermediate dose for the next level of investigation.

5\) \*Maximum Dose Level: If the dose escalation reaches the highest level of 24 mg/kg without establishing an MTD, the MTD and/or the (potential) RP2D or effective dose may be confirmed based on safety, tolerability and efficacy data obtained. Additionally, it may be decided whether new dose levels are required for further escalation studies.

After all subjects in each dose level have completed the DLT assessment, the SRC will decide whether to proceed with dose escalation, explore intermediate/higher doses, terminate the dose escalation study, proceed with a dose extension study or adjust the tumor type for dose extension, etc., based on the data obtained on safety, tolerability and antitumor activity (if required), etc. The SRC may also adjust the dose and frequency of administration, etc.; the SRC may also decide during a dose escalation whether to adjust the tumor type enrolled. Based on the provision of a reasonable basis, appropriate methods may be used to combine the pre-adjustment data with the post-adjustment data, or with data obtained from studies conducted by HCB101.

During the dose-escalation phase, if a subject does not experience a Grade ≥ 2 AE related to the trial treatment (including HCB101 or in combination with standard-of-care drugs), intra-subject dose escalation is permitted after the DLT evaluation period. A maximum of two intra-individual dose escalations per subject is allowed.

Conditions

• GC/GEJC

Interventions

BIOLOGICAL

Zolbetuximab

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.

DRUG

Oxaliplatin + 5-Fluorouracil/Leucovorin

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.

DRUG

CAPOX (oxaliplatin/capecitabine)

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.

Sponsors & Collaborators

• FBD Biologics Limited

  collaborator INDUSTRY

• China Medical University Hospital

  collaborator OTHER

• Chi Mei Medical Hospital

  collaborator OTHER

• Kaohsiung Medical University Chung-Ho Memorial Hospital

  lead OTHER

Study Design

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2026-06-30

Primary Completion

2027-12-31

Completion

2027-12-31