A Phase I/II Study of FG-M108 Plus FG-B901 in Advanced CLDN18.2-Positive Solid Tumors

Official title

An Open-Label, Multicenter Phase I/II Clinical Trial to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of FG-M108 Injection in Combination With FG-B901 Injection in Patients With Unresectable Locally Advanced or Metastatic Solid Tumors

Overview

This open-label, multicenter Phase I/II trial evaluates the combination of FG-M108 and FG-B901 in patients with unresectable locally advanced or metastatic solid tumors that are positive for Claudin 18.2 and have progressed on, are intolerant to, or lack standard therapy. The Phase I dose-escalation part (using a BF-BOIN design) assesses safety, tolerability, and pharmacokinetics, and determines the recommended Phase II dose (RP2D) of FG-B901 when given with fixed-dose FG-M108. The Phase IIa expansion cohorts, grouped by tumor type, further evaluate safety and preliminary efficacy, with antitumor activity measured by RECIST 1.1 and iRECIST, while also exploring biomarker correlates. Key eligibility requires CLDN18.2 positivity (≥10% tumor cells with ≥1+ membrane staining by IHC), ECOG performance status 0-1, and measurable disease. Up to approximately 30 participants will be enrolled per cohort in Phase IIa. The study aims to provide initial evidence on the combination's safety, tolerability, PK, immunogenicity, and clinical activity in this hard-to-treat population.

Interventions

• Drug FG-B901
  Accelerated titration method, IV infusion Q3W; Adaptive BOIN design, IV infusion Q3W. (21-day cycles)
• Drug FG-B901
  1\~2 dose levels of FG-B901 will be tested according to an accelerated titration method followed by a adaptive BOIN design
• Drug FG-M108
  300 mg/m2, IV infusion Q3W (21-day cycles)

Primary outcome measures

• Safety assessed by Adverse Events (AEs) [Time frame: Up to 24 months]
• Objective Response Rate (ORR) [Time frame: Up to 24 months]
• Disease control rate (DCR) [Time frame: Up to 24 months]

Secondary outcome measures (7)

• Progression Free Survival (PFS) [Time frame: Up to 24 months]
• Duration Of Response (DOR) [Time frame: Up to 24 months]
• Overall Survival (OS) [Time frame: Up to 24 months]
• Time to progression (TTP) [Time frame: Up to 24 months]
• Maximum measured plasma concentration of FG-B901 and FG-M108 [Time frame: Up to 24 months]
• Time to maximum plasma concentration of FG-B901 and FG-M108 [Time frame: Up to 24 months]
• Half-life of FG-B901 and FG-M108 [Time frame: Up to 24 months]

Eligibility criteria

Inclusion criteria

• Voluntarily sign the informed consent form, understand the study, are willing to comply with and have the ability to complete all trial procedures;
• Age 18-75 years (inclusive), any gender;
• Have histologically or cytologically confirmed locally advanced or metastatic solid tumors, and have failed standard therapy, or are intolerant to standard therapy, or for whom standard therapy is not available;
• CLDN18.2 positive (defined as ≥10% of tumor cells showing membrane staining ≥1+ by central laboratory IHC)
• ECOG 0-1
• Expected survival ≥3 months;
• Have at least one measurable tumor lesion according to RECIST 1.1 criteria;
• Adequate cardiac, bone marrow, liver, renal function;

Exclusion criteria

• Have received a live vaccine within 3 months prior to the first dose;
• Received radiotherapy within 4 weeks before the first dose
• Received Chinese herbal medicine with antitumor indications within 2 weeks before the first dose
• Previously received any therapy targeting CLDN18.2
• History of other malignancies within 3 years before the first dose
• Experienced Grade ≥3 immune-related adverse events (irAEs) from prior immunotherapy or discontinued immunotherapy due to irAEs, or have irAEs from prior immunotherapy that the investigator judges to still have clinical impact
• Toxicity from prior antitumor therapy has not recovered to NCI CTCAE v5.0 Grade 0-1
• History of severe allergic reactions, or hypersensitivity, or intolerance to any known component of the investigational products or other monoclonal antibodies
• Have brain or leptomeningeal metastases with symptoms
• Presence of clinically symptomatic body cavity effusions (pleural effusion, ascites, pericardial effusion, etc.) requiring local therapy or repeated drainage, or effusions that are poorly controlled per investigator judgment
• Uncontrolled or clinically significant cardiovascular and cerebrovascular diseases
• Clinically uncontrolled diseases such as diabetes, thyroid disorders (hormone replacement therapy does not affect enrollment), or other severe systemic diseases requiring systemic treatment
• Active or progressive infection requiring systemic treatment within 2 weeks before the first dose
• Known or suspected active autoimmune disease requiring systemic treatment
• Pregnant or breastfeeding female participants
• Known history of Hepatitis C or chronic active Hepatitis B

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Sequential

Masking

Open label

Primary purpose

Treatment

Study locations

China · 2 centers

• Harbin Medical University Cancer Hospital — Ha’erbin
• The First Hospital of China Medical University — Shenyang

Identifiers

NCT: NCT07704866 · FG-B901-02

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗