This is a Phase 1, open-label, dose-escalation, single-center study of ADG106 in subjects with advanced or metastatic solid tumors and/or relapsed/ refractory non-Hodgkin lymphoma. ADG106 is a fully human ligand-blocking, agonistic anti-CD137 IgG4 mAb. It binds to the activated human T cells via a T cell receptor CD137. ADG106 administered intravenously (IV) over a period of 60-90 minutes. Primary objective: To assess safety and tolerability at increasing dose levels of single agent ADG106 in subjects with advanced or metastatic solid tumors and/or non Hodgkin lymphoma. To determine the recommended dosage and dosage regimen for further study. Secondary Objectives To characterize the pharmacokinetic (PK) profiles of ADG106. To evaluate the immunogenicity of ADG106. To evaluate the potential anti-tumor effect of ADG106. To investigate serum biomarkers related to immune regulation and cytokine releasing. Exploratory Objective: To identify the potential biomarkers of ADG106.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
62
IV infusion over 60 minutes on Day 1 of each cycle, at 7 doses depending on cohort at enrollment.
Sun Yat-sen University Cancer Center
Guangzhou, Guangdong, China
Shanghai Dongfang Hospital
Shanghai, Shanghai Municipality, China
DLTs in the first 2 cycles of single drug administration
Time frame: 2 Cycles (42 days)
Number of clinical and laboratory adverse events (AEs) .
Time frame: First dose to 30 days post last dose
Objective response rate (ORR) as assessed by RECIST version 1.1 and immune-related RECIST (irRECIST) for solid tumor and the Lugano Classification for non-Hodgkin Lymphoma
Time frame: 2 Cycles (42 days)
Duration of response (DOR) as assessed by RECIST version 1.1 and immune-related RECIST (irRECIST) for solid tumor and the Lugano Classification for non-Hodgkin Lymphoma
Time frame: 2 Cycles (42 days)
Time to progression (TTP) as assessed by RECIST version 1.1 and immune-related RECIST (irRECIST) for solid tumor and the Lugano Classification for non-Hodgkin Lymphoma
Time frame: 2 Cycles (42 days)
Disease control rate (DCR) as assessed by RECIST version 1.1 and immune-related RECIST (irRECIST) for solid tumor and the Lugano Classification for non-Hodgkin Lymphoma
Time frame: 2 Cycles (42 days)
Progression-free survival (PFS) as assessed by RECIST version 1.1 and immune-related RECIST (irRECIST) for solid tumor and the Lugano Classification for non-Hodgkin Lymphoma
Time frame: 2 Cycles (42 days)
Peak plasma concentration (Cmax)
Time frame: 2 Cycles (42 days)
Plasma concentration at the end of a dosing interval (Ctrough)
Time frame: 2 Cycles (42 days)
Time to reach Cmax (Tmax)
Time frame: 2 Cycles (42 days)
Area under the curve from time zero to the last timepoint (AUC0-last)
Time frame: 2 Cycles (42 days)
AUC from time zero to infinity (AUC0-∞)
Time frame: 2 Cycles (42 days)
AUC during a dosing interval (AUCtau)
Time frame: 2 Cycles (42 days)
Clearance (CL)
Time frame: 2 Cycles (42 days)
Volume of distribution at steady state (Vss)
Time frame: 2 Cycles (42 days)
ADA levels for ADG106.
Time frame: 2 Cycles (42 days)
Serum biomarkers linked to immunomodulation and cytokine release: such as TNFα, IFN-γ, IL 10, IL-6, IL-4, IL-2.
Time frame: 2 Cycles (42 days)
Cell counts for circulating T, natural killer (NK), and B cells.
Time frame: 2 Cycles (42 days)
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