<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/NCT04501276</url>
  </required_header>
  <id_info>
    <org_study_id>ADG116-1003</org_study_id>
    <nct_id>NCT04501276</nct_id>
  </id_info>
  <brief_title>A Phase 1b/2 Study of ADG116, ADG116 Combined With Anti-PD-1 Antibody or Anti-CD137 Antibody in Solid Tumors Patients</brief_title>
  <official_title>A Phase 1b/2, Open-Label, Dose Escalation and Expansion Study of ADG116, ADG116 Combined With Toripalimab (Anti-PD-1 Antibody), ADG116 Combined With ADG106 (Anti-CD137 Antibody) in Patients With Advanced/Metastatic Solid Tumors</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Adagene Inc</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Adagene Inc</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</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 study in patients with advanced/metastatic&#xD;
      solid tumors. Study drug, ADG116, is an anti -CTLA-4 fully human monoclonal antibody that&#xD;
      specifically binds to human CTLA-4. ADG106, a fully human ligand-blocking agonistic&#xD;
      anti-CD137 IgG4 mAb, is expected to enhance the activity of activated T cells. The enhanced&#xD;
      antitumor efficacy results observed from the preclinical studies of ADG116 in combination&#xD;
      with ADG106 or anti-PD-1 provided further support to explore such combinations in clinical&#xD;
      settings for better patient responses.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">September 23, 2020</start_date>
  <completion_date type="Anticipated">January 7, 2024</completion_date>
  <primary_completion_date type="Anticipated">August 18, 2023</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Sequential Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of participants experiencing dose-limiting toxicities escalating dose levels in adults with advanced / metastatic solid tumors</measure>
    <time_frame>From first dose of ADG116 (Week 1 Day 1) until 21 days</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of participants with adverse events as assessed by CTCAE v5.0</measure>
    <time_frame>From first dose of ADG116 (Week 1 Day 1) to 28 days post last dose</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Area under the time concentration curve (AUC) from time zero to infinity (AUC0-inf)</measure>
    <time_frame>From first dose (Cycle 1 Day 1, ) until the last dose (up to 2 years)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maximum (peak) plasma concentration (Cmax)</measure>
    <time_frame>From first dose (Cycle 1 Day 1,) until the last dose (up to 2 years)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to maximum (peak) plasma concentration (Tmax)</measure>
    <time_frame>From first dose (Cycle 1 Day 1,) until the last dose (up to 2 years)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Trough plasma concentration (Ctrough)</measure>
    <time_frame>From first dose (Cycle 1 Day 1,) until the last dose (up to 2 years)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of ADAs</measure>
    <time_frame>From first dose (Cycle 1 Day 1,) until the last dose (up to 2 years)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Preliminary evidence of antitumor activity as characterized by objective response rate (ORR), disease control rate (DCR), duration of response (DOR), duration of stable disease, progression free survival (PFS), and overall survival (OS).</measure>
    <time_frame>From first dose of ADG116 (Week 1 Day 1) to 28 days post last dose</time_frame>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Anticipated">77</enrollment>
  <condition>Advanced/Metastatic Solid Tumors</condition>
  <arm_group>
    <arm_group_label>Part A : Dose escalation of ADG116 monotherapy</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Part B : Dose escalation of ADG116 combined with anti PD1 drug</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Part C : Dose escalation of ADG116 combined with ADG106</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>ADG116</intervention_name>
    <description>For monotherapy ADG116 (Part A), ADG116 will be administered IV over 60 90 minutes until disease progression, intolerable toxicities, or withdrawal of consent, or up to 2 years.</description>
    <arm_group_label>Part A : Dose escalation of ADG116 monotherapy</arm_group_label>
    <arm_group_label>Part B : Dose escalation of ADG116 combined with anti PD1 drug</arm_group_label>
    <arm_group_label>Part C : Dose escalation of ADG116 combined with ADG106</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>ADG106</intervention_name>
    <description>For the ADG116-ADG106 combination regimen, ADG116 and ADG106 will be administered until disease progression, intolerable toxicities, or withdrawal of consent, or up to 2 years.</description>
    <arm_group_label>Part C : Dose escalation of ADG116 combined with ADG106</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>anti PD1 drug</intervention_name>
    <description>For the ADG116-anti PD1 combination regimen, ADG116 and anti PD1 will be administered until disease progression, intolerable toxicities, or withdrawal of consent, or up to 2 years.</description>
    <arm_group_label>Part B : Dose escalation of ADG116 combined with anti PD1 drug</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Patients must meet all of the following inclusion criteria to be eligible for participation&#xD;
        in this study:&#xD;
&#xD;
          1. ≥ 18 years of age at the time of informed consent.&#xD;
&#xD;
          2. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.&#xD;
&#xD;
          3. Patients with advanced or metastatic solid tumors, who have progressed after all&#xD;
             standard therapies, or for whom no further standard therapy exists.&#xD;
&#xD;
          4. At least 1 measurable lesion at baseline according to the definition of RECIST v1.1.&#xD;
&#xD;
          5. Adequate organ function.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        • Patients who meet any of the following criteria cannot be enrolled:&#xD;
&#xD;
          1. Pregnant or breastfeeding females.&#xD;
&#xD;
          2. Childbearing potential who does not agree to the use of contraception during the&#xD;
             treatment period..&#xD;
&#xD;
          3. Treatment with any investigational drug within washout period.&#xD;
&#xD;
          4. Grade ≥ 3 immune-related AEs (irAEs) or irAE that lead to discontinuation of prior&#xD;
             immunotherapy.&#xD;
&#xD;
          5. Central nervous system disease involvement&#xD;
&#xD;
          6. History or risk of autoimmune disease.&#xD;
&#xD;
          7. History of life-threatening hypersensitivity or known to be allergic to protein drugs&#xD;
             or recombinant proteins or any ingredients contained in the ADG116 drug formulation.&#xD;
&#xD;
          8. Patients requiring systemic treatment with corticosteroids&#xD;
&#xD;
          9. Patients receiving granulocyte colony stimulating factor (G-CSF), within 14 days prior&#xD;
             to the first dose of the study drug.&#xD;
&#xD;
         10. Any uncontrolled active infections requiring systemic antimicrobial treatment (viral,&#xD;
             bacterial, or other), or uncontrolled or poorly controlled, asthma, chronic&#xD;
             obstructive pulmonary disease (COPD).&#xD;
&#xD;
         11. Major surgery within 4 weeks prior to the first dose of the study drug.&#xD;
&#xD;
         12. Has had an allogeneic tissue/solid organ transplant.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>Kristine She</last_name>
    <phone>4088389296</phone>
    <email>kristine_she@adagene.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Jiping Zha</last_name>
    <phone>(650)785-9347</phone>
    <email>jiping_zha@adagene.com</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Next Oncology</name>
      <address>
        <city>San Antonio</city>
        <state>Texas</state>
        <zip>78229</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Anthony Tolcher</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Ashford Cancer Centre Research</name>
      <address>
        <city>Kurralta Park</city>
        <country>Australia</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Francis Parnis</last_name>
      <email>fparnis@adelaidecancercentre.com.au</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Cabrini Hospital</name>
      <address>
        <city>Malvern</city>
        <country>Australia</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Gary Richardson</last_name>
      <email>gary.richardson@ocv.net.au</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Macquarie University</name>
      <address>
        <city>Sydney</city>
        <country>Australia</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>John Park</last_name>
      <email>john.park@mqhealth.org.au</email>
    </contact>
  </location>
  <location_countries>
    <country>Australia</country>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Brahmer JR, Lacchetti C, Schneider BJ, Atkins MB, Brassil KJ, Caterino JM, Chau I, Ernstoff MS, Gardner JM, Ginex P, Hallmeyer S, Holter Chakrabarty J, Leighl NB, Mammen JS, McDermott DF, Naing A, Nastoupil LJ, Phillips T, Porter LD, Puzanov I, Reichner CA, Santomasso BD, Seigel C, Spira A, Suarez-Almazor ME, Wang Y, Weber JS, Wolchok JD, Thompson JA; National Comprehensive Cancer Network. Management of Immune-Related Adverse Events in Patients Treated With Immune Checkpoint Inhibitor Therapy: American Society of Clinical Oncology Clinical Practice Guideline. J Clin Oncol. 2018 Jun 10;36(17):1714-1768. doi: 10.1200/JCO.2017.77.6385. Epub 2018 Feb 14.</citation>
    <PMID>29442540</PMID>
  </reference>
  <reference>
    <citation>Melero I, Hervas-Stubbs S, Glennie M, Pardoll DM, Chen L. Immunostimulatory monoclonal antibodies for cancer therapy. Nat Rev Cancer. 2007 Feb;7(2):95-106. doi: 10.1038/nrc2051.</citation>
    <PMID>17251916</PMID>
  </reference>
  <reference>
    <citation>Finn OJ. Immuno-oncology: understanding the function and dysfunction of the immune system in cancer. Ann Oncol. 2012 Sep;23 Suppl 8(Suppl 8):viii6-9. doi: 10.1093/annonc/mds256.</citation>
    <PMID>22918931</PMID>
  </reference>
  <verification_date>April 2023</verification_date>
  <study_first_submitted>July 29, 2020</study_first_submitted>
  <study_first_submitted_qc>August 2, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">August 6, 2020</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>Advanced/Metastatic Solid Tumors</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Neoplasms</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/NCT04501276
org study id: ADG116-1003
nct id: NCT04501276
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This is a Phase 1, open-label, dose escalation study in patients with advanced/metastatic
      solid tumors. Study drug, ADG116, is an anti -CTLA-4 fully human monoclonal antibody that
      specifically binds to human CTLA-4. ADG106, a fully human ligand-blocking agonistic
      anti-CD137 IgG4 mAb, is expected to enhance the activity of activated T cells. The enhanced
      antitumor efficacy results observed from the preclinical studies of ADG116 in combination
      with ADG106 or anti-PD-1 provided further support to explore such combinations in clinical
      settings for better patient responses.
allocation: Non-Randomized
intervention model: Sequential Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Number of participants experiencing dose-limiting toxicities escalating dose levels in adults with advanced / metastatic solid tumors
time frame: From first dose of ADG116 (Week 1 Day 1) until 21 days
measure: Number of participants with adverse events as assessed by CTCAE v5.0
time frame: From first dose of ADG116 (Week 1 Day 1) to 28 days post last dose
measure: Area under the time concentration curve (AUC) from time zero to infinity (AUC0-inf)
time frame: From first dose (Cycle 1 Day 1, ) until the last dose (up to 2 years)
measure: Maximum (peak) plasma concentration (Cmax)
time frame: From first dose (Cycle 1 Day 1,) until the last dose (up to 2 years)
measure: Time to maximum (peak) plasma concentration (Tmax)
time frame: From first dose (Cycle 1 Day 1,) until the last dose (up to 2 years)
measure: Trough plasma concentration (Ctrough)
time frame: From first dose (Cycle 1 Day 1,) until the last dose (up to 2 years)
measure: Incidence of ADAs
time frame: From first dose (Cycle 1 Day 1,) until the last dose (up to 2 years)
measure: Preliminary evidence of antitumor activity as characterized by objective response rate (ORR), disease control rate (DCR), duration of response (DOR), duration of stable disease, progression free survival (PFS), and overall survival (OS).
time frame: From first dose of ADG116 (Week 1 Day 1) to 28 days post last dose
arm group label: Part A : Dose escalation of ADG116 monotherapy
arm group type: Experimental
arm group label: Part B : Dose escalation of ADG116 combined with anti PD1 drug
arm group type: Experimental
arm group label: Part C : Dose escalation of ADG116 combined with ADG106
arm group type: Experimental
intervention type: Drug
intervention name: ADG116
description: For monotherapy ADG116 (Part A), ADG116 will be administered IV over 60 90 minutes until disease progression, intolerable toxicities, or withdrawal of consent, or up to 2 years.
arm group label: Part A : Dose escalation of ADG116 monotherapy
arm group label: Part B : Dose escalation of ADG116 combined with anti PD1 drug
arm group label: Part C : Dose escalation of ADG116 combined with ADG106
intervention type: Drug
intervention name: ADG106
description: For the ADG116-ADG106 combination regimen, ADG116 and ADG106 will be administered until disease progression, intolerable toxicities, or withdrawal of consent, or up to 2 years.
arm group label: Part C : Dose escalation of ADG116 combined with ADG106
intervention type: Drug
intervention name: anti PD1 drug
description: For the ADG116-anti PD1 combination regimen, ADG116 and anti PD1 will be administered until disease progression, intolerable toxicities, or withdrawal of consent, or up to 2 years.
arm group label: Part B : Dose escalation of ADG116 combined with anti PD1 drug
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Kristine She
phone: 4088389296
email: kristine_she@adagene.com
last name: Jiping Zha
phone: (650)785-9347
email: jiping_zha@adagene.com
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
country: Australia
country: United States
citation: Brahmer JR, Lacchetti C, Schneider BJ, Atkins MB, Brassil KJ, Caterino JM, Chau I, Ernstoff MS, Gardner JM, Ginex P, Hallmeyer S, Holter Chakrabarty J, Leighl NB, Mammen JS, McDermott DF, Naing A, Nastoupil LJ, Phillips T, Porter LD, Puzanov I, Reichner CA, Santomasso BD, Seigel C, Spira A, Suarez-Almazor ME, Wang Y, Weber JS, Wolchok JD, Thompson JA; National Comprehensive Cancer Network. Management of Immune-Related Adverse Events in Patients Treated With Immune Checkpoint Inhibitor Therapy: American Society of Clinical Oncology Clinical Practice Guideline. J Clin Oncol. 2018 Jun 10;36(17):1714-1768. doi: 10.1200/JCO.2017.77.6385. Epub 2018 Feb 14.
PMID: 29442540
citation: Melero I, Hervas-Stubbs S, Glennie M, Pardoll DM, Chen L. Immunostimulatory monoclonal antibodies for cancer therapy. Nat Rev Cancer. 2007 Feb;7(2):95-106. doi: 10.1038/nrc2051.
PMID: 17251916
citation: Finn OJ. Immuno-oncology: understanding the function and dysfunction of the immune system in cancer. Ann Oncol. 2012 Sep;23 Suppl 8(Suppl 8):viii6-9. doi: 10.1093/annonc/mds256.
PMID: 22918931
responsible party type: Sponsor
mesh term: Neoplasms
sharing ipd: No