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
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 入组人数
- 120
- 试验地点
- 2
- 主要终点
- Safety assessed by Adverse Events (AEs)
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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)
- •Expected survival ≥3 months;
- •Have at least one measurable tumor lesion according to RECIST 1.1 criteria;
- •Adequate cardiac, bone marrow, liver, renal function;
排除标准
- •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
结局指标
主要结局
Safety assessed by Adverse Events (AEs)
时间窗: Up to 24 months
An AE is any adverse medical event that occurs during a clinical study, whether or not related with medicinal product, including signs, symptoms, abnormal laboratory test results and diseases. The incidence and severity of AEs during the clinical study are recorded and analyzed.
Objective Response Rate (ORR)
时间窗: Up to 24 months
ORR is defined as the proportion of participants who have a best overall response of Complete Response (CR) or Partial Response (PR) as assessed by investigator evaluation per RECIST 1.1.
Disease control rate (DCR)
时间窗: Up to 24 months
DCR is defined as the proportion of participants who have a best overall response of Complete Response (CR), Partial Response (PR), or Stable Disease (SD) as assessed by investigator evaluation per RECIST 1.1.
次要结局
- Time to maximum plasma concentration of FG-B901 and FG-M108(Up to 24 months)
- Half-life of FG-B901 and FG-M108(Up to 24 months)
- Progression Free Survival (PFS)(Up to 24 months)
- Duration Of Response (DOR)(Up to 24 months)
- Overall Survival (OS)(Up to 24 months)
- Time to progression (TTP)(Up to 24 months)
- Maximum measured plasma concentration of FG-B901 and FG-M108(Up to 24 months)