A Phase Ib/II Study of AK104#PD-1 / CTLA-4 Bispecific Antibody# and AK117#Anti-CD47 Antibody# in Combination With or Without Chemotherapy in Advanced Malignant Tumors
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 128
- 试验地点
- 1
- 主要终点
- Number of patients with Adverse Events (AEs)
研究概览
简要总结
Phase Ib/II open label, multicenter study to evaluate the efficacy and safety of AK104 (anti-PD-1 and CTLA-4 bispecific antibody) and AK117#AntiCD47 Antibody# combined with or without chemotherapy in advanced malignant tumors
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 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
- •18 to 75 years old.
- •Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or
- •Have a life expectancy of at least 3 months.
- •Phase Ib: Histologically or cytologically confirmed advanced solid tumor.
- •Phase II: Has histologically confirmed diagnosis of unresectable locally advanced,recurrent or metastatic gastric or GEJ adenocarcinoma or Esophageal squamous cell carcinoma.
- •Have at least one measurable lesion based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 assessed by investigator.
- •Has adequate organ function.
排除标准
- •Undergone major surgery within 30 days prior to the first dose of study treatment.
- •Active central nervous system (CNS) metastases.
- •History of active autoimmune disease that has required systemic treatment in the past 2 years (i.e.,corticosteroids or immunosuppressive drugs).
- •Active Hepatitis B or Hepatitis C.
- •Received previous immunotherapy, including immune checkpoint inhibitors, immune checkpoint agonists, immune cell therapy and other treatments targeting the mechanism of tumor immunity.
- •History of severe bleeding tendency or coagulation disorder.
研究组 & 干预措施
Phase II#Cohort 2#
Esophageal squamous cell cancer: AK104 + 5-FU/Paclitaxel+Cisplatin± AK117 every 3- week cycle (Q3W) until progression
干预措施: AK117 (Drug)
Phase II#Cohort 3#
Gastric Cancer or Gastroesophageal Junction Cancer or Esophageal squamous cell cancer: AK117 +Paclitaxel/Docetaxel/Irinotecan every 3- or 4- week cycle (Q3W or Q4W) until progression
干预措施: AK117 (Drug)
Phase Ib#Dosage regimen 1#
Subjects receive AK104 plus AK117 every 3- week cycle (Q3W) until progression
干预措施: AK117 (Drug)
Phase Ib#Dosage regimen 1#
Subjects receive AK104 plus AK117 every 3- week cycle (Q3W) until progression
干预措施: AK104 (Drug)
Phase Ib#Dosage regimen 2#
Subjects receive AK104 plus AK117 every 6- week cycle (Q6W) until progression
干预措施: AK104 (Drug)
Phase II#Cohort 1#
Gastric Cancer or Gastroesophageal Junction Cancer: AK104 + XELOX (Oxaliplatin + Capecitabine)+AK117 every 3- week cycle (Q3W) until progression
干预措施: AK104 (Drug)
Phase II#Cohort 2#
Esophageal squamous cell cancer: AK104 + 5-FU/Paclitaxel+Cisplatin± AK117 every 3- week cycle (Q3W) until progression
干预措施: Cisplatin (Drug)
Phase II#Cohort 1#
Gastric Cancer or Gastroesophageal Junction Cancer: AK104 + XELOX (Oxaliplatin + Capecitabine)+AK117 every 3- week cycle (Q3W) until progression
干预措施: Oxaliplatin (Drug)
Phase II#Cohort 2#
Esophageal squamous cell cancer: AK104 + 5-FU/Paclitaxel+Cisplatin± AK117 every 3- week cycle (Q3W) until progression
干预措施: AK104 (Drug)
Phase II#Cohort 2#
Esophageal squamous cell cancer: AK104 + 5-FU/Paclitaxel+Cisplatin± AK117 every 3- week cycle (Q3W) until progression
干预措施: Paclitaxel (Drug)
Phase II#Cohort 2#
Esophageal squamous cell cancer: AK104 + 5-FU/Paclitaxel+Cisplatin± AK117 every 3- week cycle (Q3W) until progression
干预措施: 5-FU (Drug)
Phase II#Cohort 3#
Gastric Cancer or Gastroesophageal Junction Cancer or Esophageal squamous cell cancer: AK117 +Paclitaxel/Docetaxel/Irinotecan every 3- or 4- week cycle (Q3W or Q4W) until progression
干预措施: Paclitaxel (Drug)
Phase II#Cohort 3#
Gastric Cancer or Gastroesophageal Junction Cancer or Esophageal squamous cell cancer: AK117 +Paclitaxel/Docetaxel/Irinotecan every 3- or 4- week cycle (Q3W or Q4W) until progression
干预措施: Docetaxel (Drug)
Phase II#Cohort 3#
Gastric Cancer or Gastroesophageal Junction Cancer or Esophageal squamous cell cancer: AK117 +Paclitaxel/Docetaxel/Irinotecan every 3- or 4- week cycle (Q3W or Q4W) until progression
干预措施: Irinotecan (Drug)
Phase Ib#Dosage regimen 2#
Subjects receive AK104 plus AK117 every 6- week cycle (Q6W) until progression
干预措施: AK117 (Drug)
Phase II#Cohort 1#
Gastric Cancer or Gastroesophageal Junction Cancer: AK104 + XELOX (Oxaliplatin + Capecitabine)+AK117 every 3- week cycle (Q3W) until progression
干预措施: Capecitabine tablets (Drug)
Phase II#Cohort 1#
Gastric Cancer or Gastroesophageal Junction Cancer: AK104 + XELOX (Oxaliplatin + Capecitabine)+AK117 every 3- week cycle (Q3W) until progression
干预措施: AK117 (Drug)
结局指标
主要结局
Number of patients with Adverse Events (AEs)
时间窗: Up to approximately 2 years
Objective Response Rate (ORR)
时间窗: Up to approximately 2 years
次要结局
- Disease control rate (DCR)(Up to approximately 2 years)
- Duration of Response (DoR)(Up to approximately 2 years)
- Time to response (TTR)(Up to approximately 2 years)
- Progression free survival (PFS)(Up to approximately 2 years)
- Minimum observed concentration (Cmin) of AK117 and AK104 at steady state(From first dose of study drug to last dose of of study drug)
- Number of subjects who develop detectable anti-drug antibodies (ADAs)(From first dose of study drug through 30 days after last dose of study drug)
- Overall survival (OS)(Up to approximately 2 years)
- Maximum observed concentration (Cmax) of AK117 and AK104(From first dose of study drug to last dose of of study drug)