A Randomized, Controlled, Open-label, Multicenter Phase III Study to Evaluate the Efficacy and Safety of ATG-022 Compared With Investigator's Choice of Treatment in Subjects With Claudin18.2-Positive Advanced Gastric or Gastroesophageal Junction Adenocarcinoma
试验速览
- 阶段
- 3 期
- 状态
- 尚未招募
- 入组人数
- 380
- 试验地点
- 113
- 主要终点
- Progression-Free Survival(PFS )
研究概览
简要总结
This is a randomized, controlled, open-label, multicenter Phase III study to evaluate the efficacy and safety of ATG-022 compared with Investigator's Choice in participants with CLDN18.2-positive advanced gastric or gastroesophageal junction adenocarcinoma.
详细描述
This study is based on the positive data for ATG-022 monotherapy in CLDN18.2-positive advanced gastric/GEJ adenocarcinoma obtained from the CLINCH study. Through PopPK and exposure-response (E-R) analysis of ATG-022, this study will use ATG-022 monotherapy at 1.8 mg/kg compared to Investigator's Choice to evaluate the efficacy and safety of the two treatment regimens in participants with advanced gastric/GEJ adenocarcinoma who have received prior second-line systemic therapy. The Investigator's Choice regimen includes two optional drugs: Docetaxel or Irinotecan. Both docetaxel and irinotecan are commonly used single-agent chemotherapy drugs in third-line treatment for gastric cancer.
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
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Provide signed and dated written informed consent (ICF) before any study-specific procedures, sampling, and analyses.
- •Age ≥ 18 years at the time of consent.
- •Histologically or cytologically confirmed unresectable locally advanced or metastatic gastric or gastroesophageal junction adenocarcinoma with positive CLDN18.2 expression.
- •Disease progression after at least second-line and no more than fourth-line systemic therapy. Prior therapy must have included a fluoropyrimidine and a platinum agent.
- •If archival tumor tissue sample obtained within 36 months prior to study participation is not available, participants should be willing to undergo a biopsy at screening.
- •Life expectancy of at least 12 weeks.
- •ECOG performance status of 0 or 1 at the time of ICF signing.
- •Adequate organ function, as evidenced by the following laboratory values (transfusion and hematopoietic growth factors are not permitted within 14 days before obtaining these laboratory values):
- •ANC ≥ 1.5 × 10⁹/L.
- •Platelet count ≥ 100 × 10⁹/L.
- •Hemoglobin ≥ 90 g/L.
- •ALT ≤ 2.5 × ULN, or ALT ≤ 5 × ULN in the presence of liver metastases.
- •AST ≤ 2.5 × ULN, or AST ≤ 5 × ULN in the presence of liver metastases.
- •Total bilirubin ≤ 1.5 × ULN.
- •Creatinine ≤ 1.5 × ULN or creatinine clearance ≥ 50 mL/min (measured or calculated per Cockcroft and Gault formula); confirmation of creatinine clearance is only required when creatinine ≥ 1.5 × ULN.
- •Coagulation: INR or PT ≤ 1.5 × ULN. aPTT ≤ 1.5 × ULN (if participant is receiving anticoagulants, the value must be within the therapeutic range for the participant's condition).
- •Males of reproductive potential and females of childbearing potential must agree to use effective contraception from the time of ICF signing until 180 days after the last dose of study drug.
排除标准
- •Known active CNS metastases and/or carcinomatous meningitis.
- •Prior treatment with CLDN18.2-targeted therapy or cell therapy, excluding CLDN18.2 monospecific monoclonal antibodies.
- •Prior treatment with any chemotherapy, immunotherapy, anti-cancer drugs, or investigational products from previous clinical studies within 28 days prior to randomization, or within the period required for the investigational product or systemic anti-cancer treatment to be cleared from the body (e.g., 5 "half-lives"), whichever is deemed most appropriate by the Investigator.
- •Received extensive radiotherapy within 28 days prior to randomization, or limited-field radiotherapy for palliative purposes within 14 days prior to the first dose of study treatment.
- •Major surgery within 28 days prior to randomization (excluding placement of vascular access) or minor surgical procedures ≤ 7 days. No waiting period is required after port-a-cath placement and drain insertion.
- •Active autoimmune disease requiring systemic treatment
- •Presence of any severe or uncontrolled systemic disease as judged by the Investigator
- •Complications or other conditions (psychological, family, social, or geographical, etc.) that, in the Investigator's opinion, could affect compliance with the protocol or make the participant unsuitable for the study.
研究组 & 干预措施
Docetaxel or Irinotecan
干预措施: Docetaxel or Irinotecan (Drug)
ATG-022
干预措施: ATG-022 (Drug)
结局指标
主要结局
Progression-Free Survival(PFS )
时间窗: From randomization to first PD or death. Tumour assessments at baseline, q6w (±1w) during treatment, q12w (±1w) after 12m, q24w (±1w) after 24m, until PD/death/study end (~228 OS events, ~1yr after LPI).
PFS is defined as the duration from randomization to the first objective documentation of PD or death from any cause
Overall Survival(OS)
时间窗: From randomization to death. Survival follow-up q3m (±14d) until death/study termination (~228 OS events).
Duration from randomization to death from any cause
次要结局
- Objective response rate (ORR)(Proportion with confirmed CR/PR. Based on tumour assessments per schedule (as above). Data cutoff at study completion.)
- Disease control rate (DCR)(Proportion with CR/PR/SD ≥3 months (confirmed by ≥2 assessments). Assessment schedule as above. Data cutoff at study completion.)
- Duration of response (DOR)(From first documented CR/PR to first PD or death. Assessment schedule same as PFS. Data cutoff at study completion.)