A Randomized, Open-label, Controlled, Multicenter Phase III Study of Hydrochloride Capsule Combined With AK105 Injection Versus Standard Second-line Chemotherapy for Advanced Gastric and Gastro-oesophageal Junction Adenocarcinoma
试验速览
- 阶段
- 3 期
- 入组人数
- 528
- 试验地点
- 45
- 主要终点
- Overall survival (OS)
研究概览
简要总结
This is a randomized, controlled, open-label, multicenter study to evaluate efficacy of AK105 injection combined with Anlotinib Hydrochloride Capsules versus standard second-line chemotherapy. Patients are treated with AK105 injection combined with Anlotinib Hydrochloride Capsules or standard second-line chemotherapy, with 1:1 random ratio.
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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Understood and signed an informed consent form; 2.Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1; Life expectancy ≥ 3 months;
- •Histopathology or cytology confirmed as metastatic or local advanced gastric and gastro-oesophageal junction adenocarcinoma;
- •First-line standard chemotherapy regimen in patients with advanced gastric or gastroesophageal junction adenocarcinoma after treatment failure;
- •Has at least one measurable lesion;
- •Weight ≥40 kg or BMI ≥18.5;
- •Adequate organ function;
- •Male or female subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 6 months after the last dose of study (such as intrauterine devices , contraceptives or condoms) ;No pregnant or breastfeeding women, and a negative pregnancy test are received within 7 days before the randomization.
排除标准
- •Histopathology confirmed as squamous cell carcinoma, carcinoid, undifferentiated carcinoma, or other gastric cancer;
- •HER2 positive;
- •Has received paclitaxel or docetaxel in the first-line treatment;
- •Has received paclitaxel or docetaxel in the neoadjuvant or adjuvant treatment regimen and have relapsed or metastasized within 6 months after the last dose;
- •Has other malignant tumors within 5 years;
- •Has used anti-angiogenic drugs such as anlotinib, apatinib, lenvatinib, sorafenib, sunitinib, bevacizumab, or related immunotherapy drugs for PD-1, PD-L1, etc;
- •Severe hypersensitivity after administration of other monoclonal antibodies;
- •Has spinal cord compression, cancerous meningitis and symptomatic brain metastasis；
- •Has adverse events caused by previous therapy except alopecia that did not recover to ≤grade 1;
- •Has received radiotherapy, chemotherapy and surgery within 4 weeks before the first dose;
- •Has gastrointestinal bleeding tendency within 4 weeks before the first dose;
- •The tumor has invaded important blood vessels and will cause fatal bleeding;
- •Has multiple factors affecting oral medication;
- •Has uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated drainage;
- •Has any active autoimmune disease or history of autoimmune disease;
- •Immunosuppressant or systemic or absorbable local hormone therapy is required to achieve the aim of immunosuppression (dose > 10mg/ day prednisone or other therapeutic hormones) and is still used within 2 weeks after the first administration;
- •Has any serious and / or uncontrolled disease;
- •Has active viral infection;
- •Has participated in other anticancer drug clinical trials within 4 weeks;
- •According to the judgement of the investigators, there are other factors that may lead to the termination of the study.
研究组 & 干预措施
Anlotinib hydrochloride capsule + AK105 injection
Anlotinib hydrochloride capsule 12mg given orally in fasting conditions, once daily in 21-day cycle (14 days on treatment from Day 1-14, 7 days off treatment from Day 15-21) plus AK105 200mg intravenously (IV) on Day 1 of each 21-day cycle.
干预措施: Anlotinib hydrochloride capsule (Drug)
Anlotinib hydrochloride capsule + AK105 injection
Anlotinib hydrochloride capsule 12mg given orally in fasting conditions, once daily in 21-day cycle (14 days on treatment from Day 1-14, 7 days off treatment from Day 15-21) plus AK105 200mg intravenously (IV) on Day 1 of each 21-day cycle.
干预措施: AK105 injection (Drug)
Standard Second-line Chemotherapy
Participants receive 80 mg/m² IV paclitaxel on Days 1, 8 and 15 of each 28-day cycle, or 75mg/m² docetaxel every 3 weeks of each 21-day cycle until disease progression or unacceptable toxicity.
干预措施: Paclitaxel injection (Drug)
Standard Second-line Chemotherapy
Participants receive 80 mg/m² IV paclitaxel on Days 1, 8 and 15 of each 28-day cycle, or 75mg/m² docetaxel every 3 weeks of each 21-day cycle until disease progression or unacceptable toxicity.
干预措施: Docetaxel injection (Drug)
结局指标
主要结局
Overall survival (OS)
时间窗: up to 45 weeks
OS defined as the time from randomization to death from any cause. Subjects who do not die at the end of the extended follow-up period, or were lost to follow-up during the study, were censored at the last date they were known to be alive.
次要结局
- Overall response rate (ORR)(up to 45 weeks)
- Progression-free survival (PFS)(up to 45 weeks)
- Disease control rate (DCR)(up to 45 weeks)
- Duration of response (DOR)(up to 45 weeks)