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

NCT03802955 | Completed Phase 1

• 1 other identifier: ADG106-1002
• Study Type: interventional
• Target: 62
• Locations: 1 country
• Sites: 2

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.

Conditions

Solid Tumor; Non-Hodgkin Lymphoma

Keywords

Solid Tumor; Non-Hodgkin Lymphoma

Outcome Measures

Primary Outcomes (1)

• DLTs in the first 2 cycles of single drug administration

  2 Cycles (42 days)

Secondary Outcomes (17)

• Number of clinical and laboratory adverse events (AEs) .

  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

  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

  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

  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

  2 Cycles (42 days)

Study Arms (1)

ADG106 Dose escalation

EXPERIMENTAL

Drug: ADG106

Interventions

ADG106 DRUG

IV infusion over 60 minutes on Day 1 of each cycle, at 7 doses depending on cohort at enrollment.

ADG106 Dose escalation

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Adagene (Suzhou) Limited: lead

Study Sites (2)

Sun Yat-sen University Cancer Center

Guangzhou, Guangdong, 510000, China

Location

Shanghai Dongfang Hospital

Shanghai, Shanghai Municipality, 200120, China

Location

Related Publications (1)

• Ma Y, Luo F, Zhang Y, Liu Q, Xue J, Huang Y, Zhao Y, Yang Y, Fang W, Zhou T, Chen G, Cao J, Chen Q, She X, Luo P, Liu G, Zhang L, Zhao H. Preclinical characterization and phase 1 results of ADG106 in patients with advanced solid tumors and non-Hodgkin's lymphoma. Cell Rep Med. 2024 Feb 20;5(2):101414. doi: 10.1016/j.xcrm.2024.101414. Epub 2024 Feb 7.

  PMID: 38330942 DERIVED

MeSH Terms

Conditions

Lymphoma, Non-Hodgkin

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 8, 2019
• First Posted: January 14, 2019
• Study Start: December 20, 2018
• Primary Completion: November 1, 2021
• Study Completion: November 1, 2021
• Last Updated: April 24, 2023

Record last verified: 2023-04

Data Sharing

• IPD Sharing: Will not share

Locations

CN (2)