A Phase 3, Multi-Center, Double-Blind, Randomized, Efficacy and Safety Study of M108 Monoclonal Antibody Plus CAPOX Versus Placebo Plus CAPOX as First-line Treatment for Claudin (CLDN) 18.2-Positive, HER2-Negative, PD-L1 CPS<5, Locally Advanced Unresectable or Metastatic Gastric or Gastroesophageal Junction (GEJ) Adenocarcinoma.
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 486
- 试验地点
- 1
- 主要终点
- Progression free survival (PFS)
研究概览
简要总结
Gastric/GEJ adenocarcinoma, which is one of the major leading causes of cancer-related deaths worldwide, is a global challenge to human health. However, standard chemotherapy has limited efficacy in advanced gastric cancer, and there is an urgent need to explore and develop new therapeutic targets and combination therapy modalities. The main purpose of this study is to explore the efficacy of M108 monoclonal antibody plus capecitabine and oxaliplatin (CAPOX) versus placebo plus CAPOX as first-line treatment measured by progression free survival (PFS). This study will also evaluate safety, tolerability, pharmacokinetics and the immunogenicity profile of M108 monoclonal antibody, as well as its effects on quality of life.
详细描述
The aim of this phase 3, double-blind, randomized, placebo-controlled study is to explore the efficacy and safety of M108 monoclonal antibody plus chemotherapy versus placebo plus chemotherapy as first-line treatment for Claudin (CLDN) 18.2-Positive, HER2-Negative, PD-L1 CPS<5, locally advanced or metastatic gastric/GEJ adenocarcinoma. Patients will be randomized in a 1:1 ration to receive M108 monoclonal antibody plus chemotherapy or placebo plus chemotherapy.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
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
- •Written informed consent
- •Histologically confirmed diagnosis of locally advanced unresectable or metastatic gastric/GEJ adenocarcinoma with no treatment previously. For patients with neoadjuvant/adjuant chemotherapy in the past, duration of last therapy to recurrence should be more than 6 months
- •At least 1 measurable site of the disease according to RECIST 1.1 criteria.
- •Positive CDLN 18.2 expression
- •Negative HER2 expression, PD-L1 CPS<5
- •ECOG performance status (PS) 0-1
- •Life expectancy > 3 months
- •Age ≥ 18 years and ≤75 years
- •Adequate haematological/ coagulation/ hepatic/ renal function
- •Men and women of childbearing age should agree to use effective contraception from the time they sign their informed consent until 3 months after the last dosing. Female subjects of childbearing age must have a negative blood beta-HCG test within 72 hours prior to first dosing.
排除标准
- •Previous radiotherapy within 4 weeks prior to the start of study treatment. (if palliative radiotherapy was given to bone metastases and the patient recovered from acute toxicity was allowed).
- •Previous anti-tumor therapy within 4 weeks prior to the start of study treatment.
- •Previous major operation within 4 weeks prior to the start of study treatment.
- •Have a prior severe allergic reaction or intolerance to known components of M108 monoclonal antibodies or other monoclonal antibodies (including humanized or chimeric antibodies); Allergic or intolerant to any component of capecitabine, oxaliplatin, etc.
- •Subject who has been treated with CLDN18.2 monoclonal/bispecific antibodies, CLDN18.2 CAR-T, CLDN18.2 ADC and any therapies that target CLDN18.
- •Subject who is in pregnant or in lactation period.
- •Other clinically significant disease which may have adversely affected the safe delivery of treatment within this study.
研究组 & 干预措施
M108 plus CAPOX
干预措施: M108 monoclonal antibody (Drug)
M108 plus CAPOX
干预措施: Oxaliplatin (Drug)
M108 plus CAPOX
干预措施: Capecitabine (Drug)
placebo plus CAPOX
干预措施: Placebo (Drug)
placebo plus CAPOX
干预措施: Oxaliplatin (Drug)
placebo plus CAPOX
干预措施: Capecitabine (Drug)
结局指标
主要结局
Progression free survival (PFS)
时间窗: From date of randomization to the date of disease progression, death or end of study, assessed up to 24 months
Compare PFS (Based on Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 by Independent Review Committee (IRC)) of patients treated with M108 monoclonal antibody or placebo plus CAPOX.
次要结局
- Safety and tolerability assessed by adverse events (AEs)(From date of randomization until 28+7 days after the last dose)
- Overall survival (OS)(From date of randomization to the date of death or end of study, assessed up to 24 months)