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Study of ADG106 With Advanced or Metastatic Solid Tumors and/or Non-Hodgkin Lymphoma

Primary Purpose

Solid Tumor, Non-Hodgkin Lymphoma

Status
Completed
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
ADG106
Sponsored by
Adagene (Suzhou) Limited
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Solid Tumor focused on measuring Solid Tumor, Non-Hodgkin Lymphoma

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Male or female, 18 years to 75 years of age at the time of consent.
  2. Provide written informed consent.
  3. Subjects with advanced and/or metastatic histologically or cytologically confirmed solid tumor and/or non-Hodgkin lymphoma who are refractory or relapsed from standard therapy and who have exhausted all available therapies.
  4. At least one measurable lesion per RECIST 1.1 for solid tumors and per Lugano Classification for non-Hodgkin lymphoma
  5. ECOG performance: 0-1
  6. Adequate organ and bone marrow function
  7. After receiving the last treatment (chemotherapy, radiotherapy, biotherapy or other research drugs), the patient had a washout period of at least 4 weeks or more than 5 half-lives, and had recovered from any toxic reaction of the previous treatment to less than 1 degree.
  8. No other concomitant antineoplastic therapy (including cell therapy)
  9. Women of childbearing potential (WOCBP) must have a negative serum pregnancy test within the 7 days prior to study drug administration.
  10. Coagulation function is basically normal, INR≤1.5
  11. Cooperative in observation of adverse events and efficacy

Exclusion Criteria:

  1. Subjects with positive HCV antibody,or active hepatitis B (HBV DNA ≥ 10000 copies/mL or 2000 IU/mL), or positive hepatitis virus and taking antiviral drugs
  2. Subjects with meningeal metastasis, or subjects with brain metastasis lesions ≥ 1 cm and untreated, or subjects with brain metastasis requiring mannitol or other dehydration therapy
  3. Infection of human immunodeficiency virus (HIV), or suffering from other acquired, congenital immunodeficiency disorders, or organ transplantation history
  4. Any active autoimmune disease or evidence-based autoimmune disease, or systemic syndrome requiring systemic steroids or immunosuppressive drugs (Except for inactive vitiligo, psoriasis, asthma/specific reactivity in children after treatment within two years, or thyroid diseases controlled by alternative therapy/non-immunosuppressive therapy)
  5. The residual toxicity of the patient's previous treatment was more than grade 1
  6. Fever body temperature above 38℃ or there are clinically obvious active infections that can affect clinical trials
  7. Overdose of glucocorticoid (>10mg/d prednisone or equivalent dose) or other immunosuppressive agents was used within one month
  8. According to the investigator, any uncontrollable serious clinical problems include but are not limited to, evidence of severe or uncontrollable systemic diseases (such as unstable or uncompensated respiratory, cardiac, liver or kidney diseases); and any unstable systemic diseases (including active infections, refractory high or drug failure Controlled hypertension (>150/100 mmHg), unstable angina pectoris, congestive heart failure, liver and kidney or metabolic diseases)
  9. A clear history of neurological or psychiatric disorders, including epilepsy or dementia
  10. Non-research-related surgical procedures performed prior to the use of research drugs in patients within 28 days
  11. Investigator do not consider he/she appropriate to participate in this study
  12. Pregnant or lactating women

Sites / Locations

  • Sun Yat-sen University Cancer Center
  • Shanghai Dongfang Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

ADG106 Dose escalation

Arm Description

Outcomes

Primary Outcome Measures

DLTs in the first 2 cycles of single drug administration

Secondary Outcome Measures

Number of clinical and laboratory adverse events (AEs) .
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
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 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
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
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
Peak plasma concentration (Cmax)
Plasma concentration at the end of a dosing interval (Ctrough)
Time to reach Cmax (Tmax)
Area under the curve from time zero to the last timepoint (AUC0-last)
AUC from time zero to infinity (AUC0-∞)
AUC during a dosing interval (AUCtau)
Clearance (CL)
Volume of distribution at steady state (Vss)
ADA levels for ADG106.
Serum biomarkers linked to immunomodulation and cytokine release: such as TNFα, IFN-γ, IL 10, IL-6, IL-4, IL-2.
Cell counts for circulating T, natural killer (NK), and B cells.

Full Information

First Posted
January 8, 2019
Last Updated
April 20, 2023
Sponsor
Adagene (Suzhou) Limited
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1. Study Identification

Unique Protocol Identification Number
NCT03802955
Brief Title
Study of ADG106 With Advanced or Metastatic Solid Tumors and/or Non-Hodgkin Lymphoma
Official Title
A Phase Ⅰ Study of ADG106 Administered in Patients With Advanced or Metastatic Solid Tumors and/or Non-Hodgkin Lymphoma
Study Type
Interventional

2. Study Status

Record Verification Date
April 2023
Overall Recruitment Status
Completed
Study Start Date
December 20, 2018 (Actual)
Primary Completion Date
November 1, 2021 (Actual)
Study Completion Date
November 1, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Adagene (Suzhou) Limited

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Solid Tumor, Non-Hodgkin Lymphoma
Keywords
Solid Tumor, Non-Hodgkin Lymphoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
62 (Actual)

8. Arms, Groups, and Interventions

Arm Title
ADG106 Dose escalation
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
ADG106
Intervention Description
IV infusion over 60 minutes on Day 1 of each cycle, at 7 doses depending on cohort at enrollment.
Primary Outcome Measure Information:
Title
DLTs in the first 2 cycles of single drug administration
Time Frame
2 Cycles (42 days)
Secondary Outcome Measure Information:
Title
Number of clinical and laboratory adverse events (AEs) .
Time Frame
First dose to 30 days post last dose
Title
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)
Title
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)
Title
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)
Title
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)
Title
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)
Title
Peak plasma concentration (Cmax)
Time Frame
2 Cycles (42 days)
Title
Plasma concentration at the end of a dosing interval (Ctrough)
Time Frame
2 Cycles (42 days)
Title
Time to reach Cmax (Tmax)
Time Frame
2 Cycles (42 days)
Title
Area under the curve from time zero to the last timepoint (AUC0-last)
Time Frame
2 Cycles (42 days)
Title
AUC from time zero to infinity (AUC0-∞)
Time Frame
2 Cycles (42 days)
Title
AUC during a dosing interval (AUCtau)
Time Frame
2 Cycles (42 days)
Title
Clearance (CL)
Time Frame
2 Cycles (42 days)
Title
Volume of distribution at steady state (Vss)
Time Frame
2 Cycles (42 days)
Title
ADA levels for ADG106.
Time Frame
2 Cycles (42 days)
Title
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)
Title
Cell counts for circulating T, natural killer (NK), and B cells.
Time Frame
2 Cycles (42 days)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Male or female, 18 years to 75 years of age at the time of consent. Provide written informed consent. Subjects with advanced and/or metastatic histologically or cytologically confirmed solid tumor and/or non-Hodgkin lymphoma who are refractory or relapsed from standard therapy and who have exhausted all available therapies. At least one measurable lesion per RECIST 1.1 for solid tumors and per Lugano Classification for non-Hodgkin lymphoma ECOG performance: 0-1 Adequate organ and bone marrow function After receiving the last treatment (chemotherapy, radiotherapy, biotherapy or other research drugs), the patient had a washout period of at least 4 weeks or more than 5 half-lives, and had recovered from any toxic reaction of the previous treatment to less than 1 degree. No other concomitant antineoplastic therapy (including cell therapy) Women of childbearing potential (WOCBP) must have a negative serum pregnancy test within the 7 days prior to study drug administration. Coagulation function is basically normal, INR≤1.5 Cooperative in observation of adverse events and efficacy Exclusion Criteria: Subjects with positive HCV antibody,or active hepatitis B (HBV DNA ≥ 10000 copies/mL or 2000 IU/mL), or positive hepatitis virus and taking antiviral drugs Subjects with meningeal metastasis, or subjects with brain metastasis lesions ≥ 1 cm and untreated, or subjects with brain metastasis requiring mannitol or other dehydration therapy Infection of human immunodeficiency virus (HIV), or suffering from other acquired, congenital immunodeficiency disorders, or organ transplantation history Any active autoimmune disease or evidence-based autoimmune disease, or systemic syndrome requiring systemic steroids or immunosuppressive drugs (Except for inactive vitiligo, psoriasis, asthma/specific reactivity in children after treatment within two years, or thyroid diseases controlled by alternative therapy/non-immunosuppressive therapy) The residual toxicity of the patient's previous treatment was more than grade 1 Fever body temperature above 38℃ or there are clinically obvious active infections that can affect clinical trials Overdose of glucocorticoid (>10mg/d prednisone or equivalent dose) or other immunosuppressive agents was used within one month According to the investigator, any uncontrollable serious clinical problems include but are not limited to, evidence of severe or uncontrollable systemic diseases (such as unstable or uncompensated respiratory, cardiac, liver or kidney diseases); and any unstable systemic diseases (including active infections, refractory high or drug failure Controlled hypertension (>150/100 mmHg), unstable angina pectoris, congestive heart failure, liver and kidney or metabolic diseases) A clear history of neurological or psychiatric disorders, including epilepsy or dementia Non-research-related surgical procedures performed prior to the use of research drugs in patients within 28 days Investigator do not consider he/she appropriate to participate in this study Pregnant or lactating women
Facility Information:
Facility Name
Sun Yat-sen University Cancer Center
City
Guangzhou
State/Province
Guangdong
ZIP/Postal Code
510000
Country
China
Facility Name
Shanghai Dongfang Hospital
City
Shanghai
State/Province
Shanghai
ZIP/Postal Code
200120
Country
China

12. IPD Sharing Statement

Plan to Share IPD
No

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Study of ADG106 With Advanced or Metastatic Solid Tumors and/or Non-Hodgkin Lymphoma

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