JS107 vs Investigator's Choice as Second-line or Later Therapy for Advanced CLDN18.2-Positive Gastricor GEJ Adenocarcinoma.
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- 入组人数
- 560
- 试验地点
- 69
- 主要终点
- BICR-PFS
研究概览
简要总结
This is a multicenter, randomized, controlled, open-label, Phase III study, designed to evaluate the efficacy and safety of JS107 versus investigator-selected therapy in the second-line or later treatment of patients with advanced gastric or gastroesophageal junction adenocarcinoma positive for CLDN18.2.
The study population consists of patients with CLDN18.2-positive, HER2-negative, locally advanced or metastatic gastric or gastroesophageal junction adenocarcinoma who have received at least one prior line of systemic therapy. The primary endpoints of the study are BICR-assessed progression-free survival and overall survival.
Number of subjects and allocation:This study plans to enroll approximately 560 subjects, who will be randomized in a 1:1 ratio to receive either JS107 (experimental group) or investigator-selected therapy (control group).
详细描述
Patients with HER2 negative G/GEJ adenocarcinoma confirmed by histology/cytology. who have received at one prior line of systemic treatment and developed PD, and the previous treatment must include fluorouracil and platinum; CLDN18.2-positive, HER2-negative.
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
- •Voluntarily participate in this study, have ICF signed after sufficient informed consent, and have good compliance.
- •Age ≥ 18 years, male or female.
- •ECOG PS 0 or
- •Expected survival period≥ 3 months.
- •Patients with HER2 negative G/GEJ adenocarcinoma confirmed by histology/cytology.
- •Patients who have received at least one prior line of systemic treatments and developed PD, and the previous treatment must include fluorouracil and platinum.
- •Fresh or archival tumor tissue (blocks of formalin-fixed, paraffin-embedded [FFPE] tissue or unstained FFPE tumor tissue sections) must be available and comfirmed CLDN18.2 positivity by for central laboratory through immunohistochemistry (IHC) before randomization.
- •Having ≥ 1 measurable lesion according to RECIST v1.1 (per investigator assessment).
- •Any AEs and/or complications caused by previous therapies including surgery or radiotherapy have been adequately resolved to Grade 0 or 1 (per NCI-CTCAE v5.0 criteria) or have been stabilized in the judgment of investigators.
排除标准
- •Previous treatment with any drug or cellular therapy targeting CLDN18.2 (except CLDN18.2 monotarget monoclonal antibody).
- •Previously treated with an ADC loaded with a tubulin inhibitor.
- •Received strong CYP3A inhibitor or inducer within 2 weeks or 5 half-lives prior to randomization, whichever is longer.
- •Use of chemotherapy, immunotherapy or other anti-tumor therapies or participation in other clinical trials within 3 weeks prior to randomization, or use of oral fluorouracil, small molecule targeted drugs or traditional Chinese medicine for gastric cancer within 2 weeks prior to randomization.
- •Major surgery (requiring general anaesthesia and >24 hours of Hospitalisation) or other clincal trial drug treatment within 4 weeks prior to randomization, or radiotherapy within 2 weeks prior to randomization.
- •Imaging demonstrating brain metastases (except patients who have completed whole brain radiotherapy or local therapy (such as surgery), have discontinued prednisone for at least 4 weeks prior to randomization, and have stable radiologically confirmed tumor lesions and no clinical symptoms of tumor during 4 weeks prior to randomization), metastases to meninges, or spinal cord compression.
- •Tumor invades important surrounding structures (e.g., large blood vessels, trachea, etc.) with high risk of rupture and hemorrhage or airway fistula, or metastases to bone with high risk of paraplegia.
- •Thromboembolic events within 3 months prior to randomization (except patients with non-pulmonary Thromboembolism who do not require treatment or have been stably treated with anticoagulants for 14 days or longer prior to randomization).
- •History of other neoplasm malignant within 5 years prior to randomization, except for neoplasm malignant cured after treatment.
- •Having active autoimmune diseases requiring systemic treatment (i.e., immunologic modulator, corticosteroid, or Immunosuppression) within 2 years prior to randomization; replacement therapy (such as thyroid hormone, Insulin, or physiologic corticosteroid replacement therapy due to adrenal or pituitary insufficiency) is not considered systemic treatment.
- •Known severe allergic reaction to any component in the investigational drug formula.
研究组 & 干预措施
Experimental group
JS107: 3mg/kg, intravenous infusion, on Day 1, with a treatment cycle of every 21 days.
干预措施: JS107 for Injection (Drug)
Control group
Including 3 treatment regimens: irinotecan, paclitaxel, and docetaxel. investigators will select one regimen based on the patient's previous treatment medications, clinical benefits, and tolerability, and the administration will follow clinical guidelines and/or clinical practices. In addition, before administration, corresponding premedications (including antiemetics, preventive anti-allergy drugs, etc.) can be given with reference to clinical guidelines or drug instructions.
Irinotecan: 150mg/m², intravenous infusion, on days 1 and 15, with a 28-day treatment cycle.
Paclitaxel: 80mg/m², intravenous infusion, on days 1, 8, and 15, with a 28-day treatment cycle.
Docetaxel: 75mg/m², intravenous infusion, on day 1, with a 21-day treatment cycle.
干预措施: Irinotecan (Drug)
Control group
Including 3 treatment regimens: irinotecan, paclitaxel, and docetaxel. investigators will select one regimen based on the patient's previous treatment medications, clinical benefits, and tolerability, and the administration will follow clinical guidelines and/or clinical practices. In addition, before administration, corresponding premedications (including antiemetics, preventive anti-allergy drugs, etc.) can be given with reference to clinical guidelines or drug instructions.
Irinotecan: 150mg/m², intravenous infusion, on days 1 and 15, with a 28-day treatment cycle.
Paclitaxel: 80mg/m², intravenous infusion, on days 1, 8, and 15, with a 28-day treatment cycle.
Docetaxel: 75mg/m², intravenous infusion, on day 1, with a 21-day treatment cycle.
干预措施: Paclitaxel (Drug)
Control group
Including 3 treatment regimens: irinotecan, paclitaxel, and docetaxel. investigators will select one regimen based on the patient's previous treatment medications, clinical benefits, and tolerability, and the administration will follow clinical guidelines and/or clinical practices. In addition, before administration, corresponding premedications (including antiemetics, preventive anti-allergy drugs, etc.) can be given with reference to clinical guidelines or drug instructions.
Irinotecan: 150mg/m², intravenous infusion, on days 1 and 15, with a 28-day treatment cycle.
Paclitaxel: 80mg/m², intravenous infusion, on days 1, 8, and 15, with a 28-day treatment cycle.
Docetaxel: 75mg/m², intravenous infusion, on day 1, with a 21-day treatment cycle.
干预措施: Docetaxel (Drug)
结局指标
主要结局
BICR-PFS
时间窗: up to 2 years
Progression-Free Survival (BICR-PFS) evaluated based on Blinded Independent Central Review (BICR) (according to the RECIST v1.1 criteria)
Overall Survival
时间窗: up to 5 years
The primary endpoint of overall survival (OS) in this multicenter, randomized, open-label Phase III study is the time from randomization to death from any cause, aiming to compare the benefit between JS107 and investigator's choice of therapy in patients with CLDN18.2-positive, HER2-negative advanced gastric or gastroesophageal junction adenocarcinoma who have received at least one prior line of systemic therapy.
次要结局
- INV-PFS(up to 2 years)
- BICR-ORR or INV-ORR(up to 2 years)
- BICR-DCR or INV -DCR(up to 2 years)
- BICR-DoR or INV -DoR(up to 2 years)
- The incidence rate and severity of AE(up to 2 years)
- Valley concentration of JS107(up to 2 years)
- anti-drug antibodies (ADA) for JS107(up to 2 years)
- Incidence of neutralizing antibodies (NAb) to JS107(up to 2 years)