A Phase Ib/II Study of AK104 and AK117 in Combination With or Without Chemotherapy in Advanced Malignant Tumors

Study Overview
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Brief Summary
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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

Official Title
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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

Conditions
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Advanced Malignant Tumors

Intervention / Treatment
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* Drug: AK104
* Drug: AK117
* Drug: Capecitabine tablets
* Drug: Oxaliplatin
* Drug: Cisplatin
* Drug: Paclitaxel
* Drug: Irinotecan
* Drug: Docetaxel
* Drug: 5-FU


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Phase Ib#Dosage regimen 1#<br>Subjects receive AK104 plus AK117 every 3- week cycle (Q3W) until progression | Drug: AK104<br>* IV infusion,Specified dose on specified days<br>Drug: AK117<br>* IV infusion,Specified dose on specified days<br>|
| Experimental: Phase Ib#Dosage regimen 2#<br>Subjects receive AK104 plus AK117 every 6- week cycle (Q6W) until progression | Drug: AK104<br>* IV infusion,Specified dose on specified days<br>Drug: AK117<br>* IV infusion,Specified dose on specified days<br>|
| Experimental: Phase II#Cohort 1#<br>Gastric Cancer or Gastroesophageal Junction Cancer: AK104 + XELOX (Oxaliplatin + Capecitabine)+AK117 every 3- week cycle (Q3W) until progression | Drug: AK104<br>* IV infusion,Specified dose on specified days<br>Drug: AK117<br>* IV infusion,Specified dose on specified days<br>Drug: Capecitabine tablets<br>* Oral,Specified dose on specified days<br>Drug: Oxaliplatin<br>* IV infusion,Specified dose on specified days<br>|
| Experimental: Phase II#Cohort 2#<br>Esophageal squamous cell cancer: AK104 + 5-FU/Paclitaxel+Cisplatin± AK117 every 3- week cycle (Q3W) until progression | Drug: AK104<br>* IV infusion,Specified dose on specified days<br>Drug: AK117<br>* IV infusion,Specified dose on specified days<br>Drug: Cisplatin<br>* IV infusion,Specified dose on specified days<br>Drug: Paclitaxel<br>* IV infusion,Specified dose on specified days<br>Drug: 5-FU<br>* IV infusion,Specified dose on specified days<br>|
| Experimental: Phase II#Cohort 3#<br>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 | Drug: AK117<br>* IV infusion,Specified dose on specified days<br>Drug: Paclitaxel<br>* IV infusion,Specified dose on specified days<br>Drug: Irinotecan<br>* IV infusion,Specified dose on specified days<br>Drug: Docetaxel<br>* IV infusion,Specified dose on specified days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients with Adverse Events (AEs) |  | Up to approximately 2 years | 
| Objective Response Rate (ORR) |  | Up to approximately 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| Overall survival (OS) |  | Up to approximately 2 years | 
| Maximum observed concentration (Cmax) of AK117 and AK104 | The endpoints for assessment of PK include serum concentrations of AK117 and AK104 at different timepoints after study drug administration. | From first dose of study drug to last dose of of study drug | 
| Minimum observed concentration (Cmin) of AK117 and AK104 at steady state | The endpoints for assessment of PK include serum concentrations of AK117 and AK104 at different timepoints after study drug administration. | From first dose of study drug to last dose of of study drug | 
| Number of subjects who develop detectable anti-drug antibodies (ADAs) | The immunogenicity of AK117 and AK104 will be assessed by summarizing the 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 |