<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03802955</url>
  </required_header>
  <id_info>
    <org_study_id>ADG106-1002</org_study_id>
    <nct_id>NCT03802955</nct_id>
  </id_info>
  <brief_title>Study of ADG106 With Advanced or Metastatic Solid Tumors and/or Non-Hodgkin Lymphoma</brief_title>
  <official_title>A Phase Ⅰ Study of ADG106 Administered in Patients With Advanced or Metastatic Solid Tumors and/or Non-Hodgkin Lymphoma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Adagene (Suzhou) Limited</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Adagene Inc</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a Phase 1, open-label, dose-escalation, single-center study of ADG106 in subjects&#xD;
      with advanced or metastatic solid tumors and/or relapsed/ refractory non-Hodgkin lymphoma.&#xD;
      ADG106 is a fully human ligand-blocking, agonistic anti-CD137 IgG4 mAb. It binds to the&#xD;
      activated human T cells via a T cell receptor CD137. ADG106 administered intravenously (IV)&#xD;
      over a period of 60-90 minutes.&#xD;
&#xD;
      Primary objective:&#xD;
&#xD;
      To assess safety and tolerability at increasing dose levels of single agent ADG106 in&#xD;
      subjects with advanced or metastatic solid tumors and/or non Hodgkin lymphoma.&#xD;
&#xD;
      To determine the recommended dosage and dosage regimen for further study. Secondary&#xD;
      Objectives To characterize the pharmacokinetic (PK) profiles of ADG106. To evaluate the&#xD;
      immunogenicity of ADG106. To evaluate the potential anti-tumor effect of ADG106. To&#xD;
      investigate serum biomarkers related to immune regulation and cytokine releasing.&#xD;
&#xD;
      Exploratory Objective:&#xD;
&#xD;
      To identify the potential biomarkers of ADG106.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">December 20, 2018</start_date>
  <completion_date type="Actual">November 1, 2021</completion_date>
  <primary_completion_date type="Actual">November 1, 2021</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Sequential Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>DLTs in the first 2 cycles of single drug administration</measure>
    <time_frame>2 Cycles (42 days)</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of clinical and laboratory adverse events (AEs) .</measure>
    <time_frame>First dose to 30 days post last dose</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>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</measure>
    <time_frame>2 Cycles (42 days)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>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</measure>
    <time_frame>2 Cycles (42 days)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>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</measure>
    <time_frame>2 Cycles (42 days)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>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</measure>
    <time_frame>2 Cycles (42 days)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>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</measure>
    <time_frame>2 Cycles (42 days)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Peak plasma concentration (Cmax)</measure>
    <time_frame>2 Cycles (42 days)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Plasma concentration at the end of a dosing interval (Ctrough)</measure>
    <time_frame>2 Cycles (42 days)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to reach Cmax (Tmax)</measure>
    <time_frame>2 Cycles (42 days)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area under the curve from time zero to the last timepoint (AUC0-last)</measure>
    <time_frame>2 Cycles (42 days)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AUC from time zero to infinity (AUC0-∞)</measure>
    <time_frame>2 Cycles (42 days)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AUC during a dosing interval (AUCtau)</measure>
    <time_frame>2 Cycles (42 days)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clearance (CL)</measure>
    <time_frame>2 Cycles (42 days)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Volume of distribution at steady state (Vss)</measure>
    <time_frame>2 Cycles (42 days)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>ADA levels for ADG106.</measure>
    <time_frame>2 Cycles (42 days)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Serum biomarkers linked to immunomodulation and cytokine release: such as TNFα, IFN-γ, IL 10, IL-6, IL-4, IL-2.</measure>
    <time_frame>2 Cycles (42 days)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cell counts for circulating T, natural killer (NK), and B cells.</measure>
    <time_frame>2 Cycles (42 days)</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">62</enrollment>
  <condition>Solid Tumor</condition>
  <condition>Non-Hodgkin Lymphoma</condition>
  <arm_group>
    <arm_group_label>ADG106 Dose escalation</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>ADG106</intervention_name>
    <description>IV infusion over 60 minutes on Day 1 of each cycle, at 7 doses depending on cohort at enrollment.</description>
    <arm_group_label>ADG106 Dose escalation</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Male or female, 18 years to 75 years of age at the time of consent.&#xD;
&#xD;
          2. Provide written informed consent.&#xD;
&#xD;
          3. Subjects with advanced and/or metastatic histologically or cytologically confirmed&#xD;
             solid tumor and/or non-Hodgkin lymphoma who are refractory or relapsed from standard&#xD;
             therapy and who have exhausted all available therapies.&#xD;
&#xD;
          4. At least one measurable lesion per RECIST 1.1 for solid tumors and per Lugano&#xD;
             Classification for non-Hodgkin lymphoma&#xD;
&#xD;
          5. ECOG performance: 0-1&#xD;
&#xD;
          6. Adequate organ and bone marrow function&#xD;
&#xD;
          7. After receiving the last treatment (chemotherapy, radiotherapy, biotherapy or other&#xD;
             research drugs), the patient had a washout period of at least 4 weeks or more than 5&#xD;
             half-lives, and had recovered from any toxic reaction of the previous treatment to&#xD;
             less than 1 degree.&#xD;
&#xD;
          8. No other concomitant antineoplastic therapy (including cell therapy)&#xD;
&#xD;
          9. Women of childbearing potential (WOCBP) must have a negative serum pregnancy test&#xD;
             within the 7 days prior to study drug administration.&#xD;
&#xD;
         10. Coagulation function is basically normal, INR≤1.5&#xD;
&#xD;
         11. Cooperative in observation of adverse events and efficacy&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Subjects with positive HCV antibody，or active hepatitis B (HBV DNA ≥ 10000 copies/mL&#xD;
             or 2000 IU/mL), or positive hepatitis virus and taking antiviral drugs&#xD;
&#xD;
          2. Subjects with meningeal metastasis, or subjects with brain metastasis lesions ≥ 1 cm&#xD;
             and untreated, or subjects with brain metastasis requiring mannitol or other&#xD;
             dehydration therapy&#xD;
&#xD;
          3. Infection of human immunodeficiency virus (HIV), or suffering from other acquired,&#xD;
             congenital immunodeficiency disorders, or organ transplantation history&#xD;
&#xD;
          4. Any active autoimmune disease or evidence-based autoimmune disease, or systemic&#xD;
             syndrome requiring systemic steroids or immunosuppressive drugs (Except for inactive&#xD;
             vitiligo, psoriasis, asthma/specific reactivity in children after treatment within two&#xD;
             years, or thyroid diseases controlled by alternative therapy/non-immunosuppressive&#xD;
             therapy）&#xD;
&#xD;
          5. The residual toxicity of the patient's previous treatment was more than grade 1&#xD;
&#xD;
          6. Fever body temperature above 38℃ or there are clinically obvious active infections&#xD;
             that can affect clinical trials&#xD;
&#xD;
          7. Overdose of glucocorticoid (&gt;10mg/d prednisone or equivalent dose) or other&#xD;
             immunosuppressive agents was used within one month&#xD;
&#xD;
          8. According to the investigator, any uncontrollable serious clinical problems include&#xD;
             but are not limited to, evidence of severe or uncontrollable systemic diseases (such&#xD;
             as unstable or uncompensated respiratory, cardiac, liver or kidney diseases); and any&#xD;
             unstable systemic diseases (including active infections, refractory high or drug&#xD;
             failure Controlled hypertension (&gt;150/100 mmHg), unstable angina pectoris, congestive&#xD;
             heart failure, liver and kidney or metabolic diseases）&#xD;
&#xD;
          9. A clear history of neurological or psychiatric disorders, including epilepsy or&#xD;
             dementia&#xD;
&#xD;
         10. Non-research-related surgical procedures performed prior to the use of research drugs&#xD;
             in patients within 28 days&#xD;
&#xD;
         11. Investigator do not consider he/she appropriate to participate in this study&#xD;
&#xD;
         12. Pregnant or lactating women&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Sun Yat-sen University Cancer Center</name>
      <address>
        <city>Guangzhou</city>
        <state>Guangdong</state>
        <zip>510000</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Shanghai Dongfang Hospital</name>
      <address>
        <city>Shanghai</city>
        <state>Shanghai</state>
        <zip>200120</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>April 2023</verification_date>
  <study_first_submitted>January 8, 2019</study_first_submitted>
  <study_first_submitted_qc>January 11, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 14, 2019</study_first_posted>
  <last_update_submitted>April 20, 2023</last_update_submitted>
  <last_update_submitted_qc>April 20, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">April 24, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Solid Tumor</keyword>
  <keyword>Non-Hodgkin Lymphoma</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lymphoma</mesh_term>
    <mesh_term>Lymphoma, Non-Hodgkin</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03802955
org study id: ADG106-1002
nct id: NCT03802955
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
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.
allocation: N/A
intervention model: Sequential Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: DLTs in the first 2 cycles of single drug administration
time frame: 2 Cycles (42 days)
measure: Number of clinical and laboratory adverse events (AEs) .
time frame: First dose to 30 days post last dose
measure: 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)
measure: 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)
measure: 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)
measure: 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)
measure: 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)
measure: Peak plasma concentration (Cmax)
time frame: 2 Cycles (42 days)
measure: Plasma concentration at the end of a dosing interval (Ctrough)
time frame: 2 Cycles (42 days)
measure: Time to reach Cmax (Tmax)
time frame: 2 Cycles (42 days)
measure: Area under the curve from time zero to the last timepoint (AUC0-last)
time frame: 2 Cycles (42 days)
measure: AUC from time zero to infinity (AUC0-∞)
time frame: 2 Cycles (42 days)
measure: AUC during a dosing interval (AUCtau)
time frame: 2 Cycles (42 days)
measure: Clearance (CL)
time frame: 2 Cycles (42 days)
measure: Volume of distribution at steady state (Vss)
time frame: 2 Cycles (42 days)
measure: ADA levels for ADG106.
time frame: 2 Cycles (42 days)
measure: 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)
measure: Cell counts for circulating T, natural killer (NK), and B cells.
time frame: 2 Cycles (42 days)
arm group label: ADG106 Dose escalation
arm group type: Experimental
intervention type: Drug
intervention name: ADG106
description: IV infusion over 60 minutes on Day 1 of each cycle, at 7 doses depending on cohort at enrollment.
arm group label: ADG106 Dose escalation
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
facility: 
facility: 
country: China
responsible party type: Sponsor
mesh term: Lymphoma
mesh term: Lymphoma, Non-Hodgkin
sharing ipd: No