Study of ADG206 in Subjects With Advanced/Metastatic Solid Tumors

Study Overview
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Brief Summary
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ADG206 is an activatable prodrug form of a fully human monoclonal antibody (mAb) of the immunoglobulin G1 (IgG1) subclass that specifically targets cluster of differentiation 137 (CD137) (also known as 4-1BB) as a co-stimulatory receptor agonist for the treatment of advanced malignancies.

Detailed Description
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This is a FIH, Phase 1, open-label, multicenter, sequential dose escalation study to evaluate the safety, tolerability, Pharmacokinetics (PK), and preliminary efficacy of ADG206 in subjects with advanced/metastatic malignancies. Primary Objective of the study: To assess safety and tolerability at increasing dose levels of ADG206 in subjects with advanced/metastatic solid tumors who have exhausted their treatment alternatives.

Official Title
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A First-in-Human (FIH), Open-Label, Phase 1 Study of ADG206, a CD137 Agonist Antibody, in Subjects With Advanced/Metastatic Solid Tumors

Conditions
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Advanced/Metastatic Solid Tumors

Intervention / Treatment
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* Drug: ADG206


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Eastern Cooperative Oncology Group (ECOG) performance status ≤1. Subjects with advanced or metastatic solid tumors (except thymic tumors), which have progressed after all standard therapies, or no further standard therapies exists. At least 1 measurable lesion per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1). Adequate organ function. Woman of childbearing potential must agree to use 2 methods of acceptable contraception from screening until 6 months after the last dose of study drug. Male subjects who are sexually active with a female partner of childbearing potential must agree to use a barrier contraception. Exclusion Criteria: Subjects within washout period of other anti-tumor therapies. . History of prior malignancy other than the cancer under treatment in the study. Major trauma or major surgery within 4 weeks before the first dose of study drug. Serious nonhealing wound, ulcer, or bone fracture. History of significant immune-mediated AE. Central nervous system (CNS) disease involvement. Any evidence of underlying severe liver dysfunction. Prior organ allograft transplantations or allogeneic bone marrow, cord blood or peripheral blood stem cell transplantation. Clinically significant cardiac disease with insufficient cardiac function. Evidence of active uncontrolled viral, bacterial, or systemic fungal infection. Known positive test result for human immunodeficiency virus (HIV) or acquired immune deficiency syndrome (AIDS). Infection of hepatitis B virus (HBV), or hepatitis C virus (HCV) (unless the disease is clinically controlled) . History or risk of autoimmune disease. Subjects with active severe lung infection or with a history of interstitial lung diseases, noninfectious pneumonitis, active pulmonary tuberculosis, or evidence of active pneumonitis. Clinically significant and unmanageable ascites defined as requiring constant therapeutic paracentesis. Any serious underlying issue that would limit compliance with study requirements, impair the ability of the subject to understand informed consent. Known hypersensitivity, allergies, or intolerance to immunoglobulins or to any excipient contained in ADG206. Pregnant, lactating, or breastfeeding.

Ages Eligible for Study
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Minimum Age: 18 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
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ADG206 dose escalation<br> | Drug: ADG206<br>* All participants in this study will receive the study drug ADG206 in one of the designed dosage level. ADG206 will be administered by intravenous infusion over 60-90 minutes on Day 1 of each treatment cycle until disease progression, intolerable toxicities or withdrawal of consent, or up to 2 years.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants experiencing dose-limiting toxicities escalating dose levels |  | At the end of Cycle 1 (each cycle is 21 days) | 
| Number of participants with adverse events (AE) |  | At the end of 90 days post last dose (each cycle is 21 days) | 
| Maximum administered dose (MAD) of ADG206 |  | At the end of the last dose (each cycle is 21 days) | 
| Maximum tolerated dose (MTD) of ADG 206 |  | At the end of the last dose (each cycle is 21 days) | 
| Recommended Phase 2 dose (RP2D) of ADG206 |  | At the end of the last dose (each cycle is 21 days) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The area under the curve (AUC) of plasma concentration of drug |  | At the end of the last dose (each cycle is 21 days) | 
| Immunogenicity endpoints include antidrug antibodies (ADAs) |  | At the end of the last dose (each cycle is 21 days) | 
| Maximum concentration (Cmax) |  | At the end of the last dose (each cycle is 21 days) | 
| Time to maximum plasma concentration (Tmax) |  | At the end of the last dose (each cycle is 21 days) | 
| Lowest plasma concentration (C[trough]) |  | At the end of the last dose (each cycle is 21 days) |