A Phase Ib/II Study of AK112 in Combination With AK117 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 AK112 (anti-PD-1 and VEGF bispecific antibody) combined with AK117#AntiCD47 Antibody# in advanced malignant tumors

Official Title
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A Phase Ib/II Study of AK112#PD-1/VEGF Bispecific Antibody# in Combination With AK117#Anti-CD47 Antibody# in Advanced Malignant Tumors

Conditions
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Advanced Malignant Tumors

Intervention / Treatment
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* Drug: AK112
* Drug: AK117
* Drug: Carboplatin
* Drug: Cisplatin
* Drug: 5-Fluorouracil


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18 to 75 years old. Have a life expectancy of at least 3 months. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Phase Ib: Histologically or cytologically confirmed selected advanced solid tumor. Phase II: Cohort 1 and 2 : A. Has histologically confirmed recurrent or metastatic HNSCC who had failed only first-line platinum-containing therapy. B. Has histologically confirmed recurrent or metastatic HNSCC with PD-L1 positive (CPS≥1) without prior systemic antitumor therapy. Cohort 3: Has histologically confirmed recurrent or metastatic HNSCC without prior systemic antitumor therapy. 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 AK112 (20 mg/kg Q3W) + AK117 (30 mg/kg QW) | Drug: AK112<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 AK112 (20 mg/kg Q3W) + AK117 (45 mg/kg QW) | Drug: AK112<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>Head and neck squamous cell carcinoma (HNSCC): AK112 (20 mg/kg Q3W) | Drug: AK112<br>* IV infusion,Specified dose on specified days<br>|
| Experimental: Phase II#Cohort 2#<br>HNSCC: AK112 (20 mg/kg Q3W) + AK117 (recommended Phase 2 dose) | Drug: AK112<br>* IV infusion,Specified dose on specified days<br>Drug: AK117<br>* IV infusion,Specified dose on specified days<br>|
| Experimental: Phase II#Cohort 3#<br>HNSCC: AK112 (20 mg/kg Q3W) + AK117 (recommended Phase 2 dose)+Carboplatin/cisplatin+5-fluorouracil | Drug: AK112<br>* IV infusion,Specified dose on specified days<br>Drug: AK117<br>* IV infusion,Specified dose on specified days<br>Drug: Carboplatin<br>* IV infusion,Specified dose on specified days<br>Drug: Cisplatin<br>* IV infusion,Specified dose on specified days<br>Drug: 5-Fluorouracil<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) | Characterization of incidence, severity and abnormal clinically significant laboratory findings of AEs | Up to approximately 2 years | 
| Number of patients experiencing dose-limiting toxicities (DLTs) |  | During the first 3 weeks | 
| 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 |