A Phase Ib/II Study of AK104 and AK117 in Combination With or Without Chemotherapy in Advanced Malignant Tumors
Phase 1
- Conditions
- Advanced Malignant Tumors
- Interventions
- Registration Number
- NCT05235542
- Lead Sponsor
- Akeso
- Brief Summary
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
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 130
Inclusion Criteria
- 18 to 75 years old.
- Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
- 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.
Exclusion Criteria
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Phase Ib#Dosage regimen 1# AK117 Subjects receive AK104 plus AK117 every 3- week cycle (Q3W) until progression Phase Ib#Dosage regimen 1# AK104 Subjects receive AK104 plus AK117 every 3- week cycle (Q3W) until progression Phase Ib#Dosage regimen 2# AK117 Subjects receive AK104 plus AK117 every 6- week cycle (Q6W) until progression Phase II#Cohort 1# AK104 Gastric Cancer or Gastroesophageal Junction Cancer: AK104 + XELOX (Oxaliplatin + Capecitabine)+AK117 every 3- week cycle (Q3W) until progression Phase II#Cohort 1# AK117 Gastric Cancer or Gastroesophageal Junction Cancer: AK104 + XELOX (Oxaliplatin + Capecitabine)+AK117 every 3- week cycle (Q3W) until progression Phase II#Cohort 1# Capecitabine tablets Gastric Cancer or Gastroesophageal Junction Cancer: AK104 + XELOX (Oxaliplatin + Capecitabine)+AK117 every 3- week cycle (Q3W) until progression Phase II#Cohort 3# AK117 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 Phase II#Cohort 2# AK117 Esophageal squamous cell cancer: AK104 + 5-FU/Paclitaxel+Cisplatin± AK117 every 3- week cycle (Q3W) until progression Phase II#Cohort 3# Paclitaxel 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 Phase Ib#Dosage regimen 2# AK104 Subjects receive AK104 plus AK117 every 6- week cycle (Q6W) until progression Phase II#Cohort 2# Cisplatin Esophageal squamous cell cancer: AK104 + 5-FU/Paclitaxel+Cisplatin± AK117 every 3- week cycle (Q3W) until progression Phase II#Cohort 1# Oxaliplatin Gastric Cancer or Gastroesophageal Junction Cancer: AK104 + XELOX (Oxaliplatin + Capecitabine)+AK117 every 3- week cycle (Q3W) until progression Phase II#Cohort 2# AK104 Esophageal squamous cell cancer: AK104 + 5-FU/Paclitaxel+Cisplatin± AK117 every 3- week cycle (Q3W) until progression Phase II#Cohort 2# Paclitaxel Esophageal squamous cell cancer: AK104 + 5-FU/Paclitaxel+Cisplatin± AK117 every 3- week cycle (Q3W) until progression Phase II#Cohort 2# 5-FU Esophageal squamous cell cancer: AK104 + 5-FU/Paclitaxel+Cisplatin± AK117 every 3- week cycle (Q3W) until progression Phase II#Cohort 3# Docetaxel 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 Phase II#Cohort 3# Irinotecan 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
- Primary Outcome Measures
Name Time Method Number of patients with Adverse Events (AEs) Up to approximately 2 years Objective Response Rate (ORR) Up to approximately 2 years
- Secondary Outcome Measures
Name Time Method 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 The endpoints for assessment of PK include serum concentrations of AK117 and AK104 at different timepoints after study drug administration.
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 The immunogenicity of AK117 and AK104 will be assessed by summarizing the number of subjects who develop detectable anti-drug antibodies (ADAs).
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 The endpoints for assessment of PK include serum concentrations of AK117 and AK104 at different timepoints after study drug administration.
Trial Locations
- Locations (1)
Shanghai Renji Hospital
🇨🇳Shanghai, China