A Study ATG-101 in Patients With Metastatic/Advanced Solid Tumors and Mature B-cell Non-Hodgkin Lymphomas

Study Overview
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Brief Summary
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This is a First-in-Human Phase I trial of ATG-101 in Patients with Metastatic/Advanced Solid Tumors and Mature B-cell Non-Hodgkin Lymphomas.

Detailed Description
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This is a First-in-Human Phase I trial of ATG-101 in Patients with Metastatic/Advanced Solid Tumors and Mature B-cell Non-Hodgkin Lymphomas. Dose Escalation Phase: Approximately 40-50 subjects with a maximum number of 62; 1-20 subjects for enhanced PDx cohort. Dose Expansion Phase: Estimated 100-400 subjects depending on the number of cohorts to be expanded.

Official Title
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A First-in-Human Phase I Trial of ATG-101 in Patients With Metastatic/Advanced Solid Tumors and Mature B-cell Non-Hodgkin Lymphomas

Conditions
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Mature B-cell Non-Hodgkin Lymphoma, Advanced Solid Tumor, Metastatic Solid Tumor

Intervention / Treatment
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* Drug: ATG-101


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Provision of signed and dated, written informed consent prior to any study-specific procedures, sampling, and analyses. Aged at least 18 years as of the date of consent. Histological or cytological confirmation of a solid tumor, and has progressed despite standard therapy, or is intolerant to standard therapy, or has a tumor for which no standard therapy exists or for which standard therapy is not considered adequate. Estimated life expectancy of a minimum of 12 weeks. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1. Female and male subjects should be using adequate contraceptive measures as requested. Exclusion Criteria: Subjects with CNS tumors or known CNS metastases will be excluded. Prior ATG-101 administration or a 4-1BB agonist. Prior anti-tumor systemic therapy within 21 days(a period of 5 'half- lives') of the first dose of study treatment. Radiotherapy with a wide field of radiation within 28 days. With the exception of alopecia, any unresolved toxicities from prior therapy greater than Grade 1 (CTCAE v5.0) at the time of ICF signature. Active infection, including hepatitis B and/or hepatitis C. Have uncontrolled intercurrent illness, including but not limited to: Inadequate bone marrow reserve or organ function. History of hypersensitivity or history of allergic reactions attributed to drugs with a similar chemical or biologic structure or class to ATG-101. Prior organ allograft transplantations. Pregnant or nursing females. Have a history of another primary malignancy within 3 years prior to starting study treatment. Exceptions are as follows: the disease under study; adequately treated basal or squamous cell carcinoma of the skin; cancer of the cervix in situ, etc. In the opinion of the investigator, subject's complications or other conditions may affect protocol compliance or may be unsuitable for participation in the study.

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: ATG-101<br>Dose Escalation Phase: Will be conducted with an enhanced PDx cohort. Dose Expansion Phase: Subjects with advanced or metastatic solid tumors and mature B-NHLs will be enrolled. | Drug: ATG-101<br>* ATG-101 will be administered intravenously once every 21 days. The dose levels will be determined by the starting dose and the escalation steps taken in the trial. The Dose Expansion Phase will begin at the defined MTD, RP2D, or biologically optimal dose.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AEs | To evaluate the safety of ATG-101. It is the responsibility of the investigator to record and document all AEs (occurring from the first dose of study treatment on C1D1) throughout the study. Clinically significant symptoms and signs related to disease progression will be reported as AEs and meet one or more of the following criteria: With clinical symptoms. Leading to the change of study treatment (eg, dose adjustment, dose interruption, or study drug withdraw). Leading to the change of concomitant treatment (eg, adding, interrupting, or terminating concomitant medications, therapies, or treatments, or any other changes). | One year after last patient first dose | 
| SAEs | To evaluate the safety of ATG-101. It is the responsibility of the investigator to record and document all SAEs (occurring from the signing of the informed consent form) throughout the study. A SAE is any untoward medical occurrence that occurs at any dose (including SAEs occurred after the ICF is signed and prior to dosing): Results in death. Is life-threatening (immediate risk of death). Requires inpatient hospitalization or prolongation of existing hospitalization. Results in persistent or significant disability/incapacity. Is a congenital anomaly/birth defect. These should also usually be considered serious. Examples of such events are intensive treatment in an emergency room or at home for allergic bronchospasm, blood dyscrasias or convulsive that do not result in hospitalization; or development of drug dependency or drug abuse. | One year after last patient first dose | 
| DLT (for Dose Escalation Phase only) | The DLTs will be evaluated during Cycle 1 of treatment. Toxicity will be graded according to the National Cancer Institute-Common Terminology Criteria for Adverse Events. The DLTs for this study may include the following: Cytokine release syndrome, Hematologic toxicity, Non-hematologic toxicity. | One year after last patient first dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ORR | To evaluate preliminary anti tumor activity of ATG-101 | One year after last patient first dose | 
| DOR | To evaluate preliminary anti tumor activity of ATG-101 | One year after last patient first dose | 
| DCR | To evaluate preliminary anti tumor activity of ATG-101 | One year after last patient first dose | 
| PFS | To evaluate preliminary anti tumor activity of ATG-101 | One year after last patient first dose | 
| OS | To evaluate preliminary anti tumor activity of ATG-101 | One year after last patient first dose | 
| The incidence of ADA and NAb | To evaluate the immunogenicity of ATG-101 | One year after last patient first dose | 
| Serum concentrations of ATG-101 and derived PK parameters (for Dose Escalation Phase only) | To characterize the PK of ATG 101 (for Dose Escalation Phase only) | One year after last patient first dose |