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

Study Description

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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. T cell is a kind of lymphocyte (a subtype of white blood cells) that protects bodies by eliminating tumor cells, and normal cells infected with viruses or bacteria. By binding to CD137, the study drug is expected to enhance the activity of activated T cells and thus stimulate a more intense immune attack to kill tumor cells. ADG106 is expected to enhance the activity of activated T cells.

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.

Condition or disease	Intervention/treatment	Phase
Solid Tumor; Non-Hodgkin Lymphoma	Drug: ADG106	Phase 1

Study Design

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	24 participants
Intervention Model:	Sequential Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	A Phase Ⅰ Study of ADG106 Administered in Patients With Advanced or Metastatic Solid Tumors and/or Non-Hodgkin Lymphoma
Actual Study Start Date :	December 20, 2018
Estimated Primary Completion Date :	December 2020
Estimated Study Completion Date :	December 2021

Arms and Interventions

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Arm	Intervention/treatment
Experimental: ADG106 Dose escalation	Drug: ADG106; IV infusion over 60 minutes on Day 1 of each cycle, at doses of 0.1 mg/kg, 0.5 mg/kg, 1.5 mg/kg, 3.0 mg/kg, 5.0 mg/kg, 7.5 mg/kg, or 10 mg/kg depending on cohort at enrollment.

Outcome Measures

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Primary Outcome Measures :

1. DLTs in the first 2 cycles of single drug administration [ Time Frame: 2 Cycles (42 days) ]

Secondary Outcome Measures :

1. Number of clinical and laboratory adverse events (AEs) . [ Time Frame: First dose to 30 days post last dose ]
2. 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) ]
3. 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) ]
4. 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) ]
5. 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) ]
6. 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) ]
7. Peak plasma concentration (Cmax) [ Time Frame: 2 Cycles (42 days) ]
8. Plasma concentration at the end of a dosing interval (Ctrough) [ Time Frame: 2 Cycles (42 days) ]
9. Time to reach Cmax (Tmax) [ Time Frame: 2 Cycles (42 days) ]
10. Area under the curve from time zero to the last timepoint (AUC0-last) [ Time Frame: 2 Cycles (42 days) ]
11. AUC from time zero to infinity (AUC0-∞) [ Time Frame: 2 Cycles (42 days) ]
12. AUC during a dosing interval (AUCtau) [ Time Frame: 2 Cycles (42 days) ]
13. Clearance (CL) [ Time Frame: 2 Cycles (42 days) ]
14. Volume of distribution at steady state (Vss) [ Time Frame: 2 Cycles (42 days) ]
15. ADA levels for ADG106. [ Time Frame: 2 Cycles (42 days) ]
16. 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) ]
17. Cell counts for circulating T, natural killer (NK), and B cells. [ Time Frame: 2 Cycles (42 days) ]

Eligibility Criteria

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Ages Eligible for Study:	18 Years to 75 Years (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

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. Provide tumor pathological section to the third party lab for PD-L1, CD137, CD137-L, MSI testing during screening period
5. At least one measurable lesion per RECIST 1.1 for solid tumors and per Lugano Classification for non-Hodgkin lymphoma
6. ECOG performance: 0-1
7. Adequate organ and bone marrow function
8. 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.
9. No other concomitant antineoplastic therapy (including cell therapy)
10. Women of childbearing potential (WOCBP) must have a negative serum pregnancy test within the 7 days prior to study drug administration.
11. Coagulation function is basically normal, INR≤1.5
12. 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

Contacts and Locations

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Contacts

Contact: Xiaohong She, Master	+8618260157039	kristine_she@adagene.com

Locations

China, Guangdong
Sun Yat-sen University Cancer Center	Recruiting
Guangzhou, Guangdong, China, 510000
Contact: Li Zhang, Master

Sponsors and Collaborators

Adagene (Suzhou) Limited

More Information

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Responsible Party:	Adagene (Suzhou) Limited
ClinicalTrials.gov Identifier:	NCT03802955 History of Changes
Other Study ID Numbers:	ADG106-1002
First Posted:	January 14, 2019
Last Update Posted:	January 14, 2019
Last Verified:	January 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD:	No

Studies a U.S. FDA-regulated Drug Product:		No
Studies a U.S. FDA-regulated Device Product:		No

Keywords provided by Adagene Inc ( Adagene (Suzhou) Limited ):

Solid Tumor; Non-Hodgkin Lymphoma

Additional relevant MeSH terms:

Lymphoma; Lymphoma, Non-Hodgkin; Neoplasms by Histologic Type; Neoplasms	Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases