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Trial record 1 of 1 for:    ADG116-1003
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A Phase 1b Study of ADG116, ADG116 Combined With Anti-PD-1 Antibody or Anti-CD137 Antibody in Solid Tumors Patients

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ClinicalTrials.gov Identifier: NCT04501276
Recruitment Status : Recruiting
First Posted : August 6, 2020
Last Update Posted : February 9, 2022
Sponsor:
Information provided by (Responsible Party):
Adagene Inc

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Advanced/Metastatic Solid Tumors Drug: ADG116 Drug: ADG106 Drug: anti PD1 drug Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 204 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1b, 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
Actual Study Start Date : September 23, 2020
Estimated Primary Completion Date : July 2023
Estimated Study Completion Date : December 2023

Arm Intervention/treatment
Experimental: Part A : Dose escalation of ADG116 monotherapy Drug: ADG116
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.

Experimental: Part B : Dose escalation of ADG116 combined with anti PD1 drug Drug: ADG116
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.

Drug: anti PD1 drug
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.

Experimental: Part C : Dose escalation of ADG116 combined with ADG106 Drug: ADG116
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.

Drug: ADG106
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.




Primary Outcome Measures :
  1. 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 ]
  2. 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 ]

Secondary Outcome Measures :
  1. 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) ]
  2. Maximum (peak) plasma concentration (Cmax) [ Time Frame: From first dose (Cycle 1 Day 1,) until the last dose (up to 2 years) ]
  3. Time to maximum (peak) plasma concentration (Tmax) [ Time Frame: From first dose (Cycle 1 Day 1,) until the last dose (up to 2 years) ]
  4. Trough plasma concentration (Ctrough) [ Time Frame: From first dose (Cycle 1 Day 1,) until the last dose (up to 2 years) ]
  5. Incidence of ADAs [ Time Frame: From first dose (Cycle 1 Day 1,) until the last dose (up to 2 years) ]
  6. 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 ]


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Patients must meet all of the following inclusion criteria to be eligible for participation in this study:

  1. ≥ 18 years of age at the time of informed consent.
  2. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 with no deterioration over the previous 2 weeks.
  3. Estimated life expectancy of more than 12 weeks.
  4. For dose escalation, patients with advanced or metastatic solid tumors, confirmed by histologically or pathologically documented (except patients with HCC, please see below for HCC requirement), who have progressed after all standard therapies, or for whom no further standard therapy exists. Patients who have declined standard therapy or have no access to standard therapy may be enrolled and the reasons for lack of access need to be documented. Patients should have at least 1 measurable lesion at baseline according to the definition of RECISTv1.1.
  5. Patients who are refractory or relapsed to prior anti-CTLA4 checkpoint inhibitors or anti programmed cell death protein 1 (PD 1) will also be recruited if they meet all eligibility criteria.
  6. Adequate hematologic function, defined by the following:

    1. Absolute neutrophil count (ANC) ≥ 1.5 ×109/L, without the use of granulocyte colony stimulating factor such as filgrastim within 2 weeks prior to study treatment.
    2. Platelet count ≥ 100 × 109/L without transfusion within 2 weeks (≤ 14 days) prior to study treatment. Patients with HCC and a platelet count ≥75 × 109/L.
    3. Hemoglobin ≥ 9 g/dL without transfusion or erythropoietin within 2 weeks (≤ 14 days) prior to study treatment.
  7. Aspartate transaminase (AST) and alanine aminotransferase (ALT) ≤ 3 × upper limit of normal (ULN), and total bilirubin ≤ 1.5 × ULN. Exception: Patients who have serum bilirubin increases due to documented underlying Gilbert's Syndrome or familial benign unconjugated hyperbilirubinemia.
  8. Adequate renal function defined by either a creatinine clearance ≥ 60 mL/min (by Cockcroft-Gault formula) or serum creatinine (SCr) < 1.5 × ULN
  9. Coagulation tests, defined by the following:

    1. Activated partial thromboplastin time (aPTT) ≤ 1.5 × ULN.
    2. International normalized ratio (INR) ≤ 1.5 × ULN. Exception: INR 2 to ≤ 3 × ULN is acceptable for patients on Warfarin anticoagulation.
  10. Left ventricular ejection fraction (LVEF) ≥ 50% measured by multiple-gated acquisition (MUGA) or echocardiogram.
  11. Previous antitumor therapy (including endocrine, chemoradiotherapy/ radiotherapy, targeted therapy, or immunotherapy) that has ended at least 4 weeks prior to administration of ADG116. Focal radiation therapy for symptom relief must have been completed at least 2 weeks prior to the first dose of ADG116.
  12. Previous AEs have been improved to baseline or Grade ≤ 1 NCI CTCAE v5.0 (except for patients with alopecia).

Exclusion Criteria:

• Patients who meet any of the following criteria cannot be enrolled:

  1. Pregnant or breastfeeding females.
  2. Females of childbearing potential and males whose partners are of childbearing potential who do not agree to the use of 2 forms of highly effective contraception during the treatment period and for 120 days after the last dose of study drug.
  3. Treatment with any investigational drug within 4 weeks prior to the first dose of study drug.
  4. Grade ≥ 3 immune-related AEs (irAEs) or irAE that lead to discontinuation of prior immunotherapy.
  5. Central nervous system disease involvement (but allow patients with prior brain metastases treated at least 4 weeks prior to the first dose of ADG116 that are clinically stable and do not require chronic corticosteroid treatment to be enrolled in the study), or prior history of NCI CTCAE Grade ≥ 3 drug-related CNS toxicity.
  6. History of life-threatening hypersensitivity or known to be allergic to protein drugs or recombinant proteins or any ingredients contained in the ADG116 drug formulation.
  7. Patients with active autoimmune disease or a documented medical history of autoimmune disease or symptoms (including celiac disease) that required systemic use of pharmacologic dose of corticosteroid and/or immunosuppressant. Exceptions are patients with vitiligo, resolved childhood asthma/atopy, and type 1 diabetes mellitus or hypothyroidism that can be managed by replacement therapy, or any other autoimmune condition upon discussion with Medical Monitor and the Sponsor.
  8. Patients requiring systemic treatment with corticosteroids (> 15 mg/day prednisone or equivalent) or other immunosuppressive medications within 21 days before the planned first dose of study drug. Inhaled or topical steroids, and adrenal replacement steroid doses ≤ 15 mg daily prednisone equivalent are permitted in the absence of active autoimmune disease. Ophthalmologic, nasal, inhaled and intra-articular injections of steroids are allowed.
  9. Peripheral neuropathy Grade ≥ 2.
  10. Patients receiving granulocyte colony stimulating factor (G-CSF), granulocyte macrophage colony stimulating factor (GM-CSF), erythropoietin, or blood (red blood cell [RBC] or platelet) transfusion within 14 days prior to the first dose of the study drug.
  11. Active viral (any etiology) hepatitis patients are excluded. Hepatitis B virus (HBV) carriers are ineligible. Cured hepatitis C (HCV) (negative HCV ribonucleic acid [RNA] test) patients may be enrolled after consulting with the Medical Monitor. This criterion does not apply for HCC.
  12. Any uncontrolled active infections requiring systemic antimicrobial treatment (viral, bacterial, or other), or uncontrolled or poorly controlled diabetes as evidenced by screening (baseline) HgbA-1c ≥7.5, asthma, chronic obstructive pulmonary disease (COPD), or other conditions that pose a risk to the patient participating on study.
  13. Known positive test result for human immunodeficiency virus (HIV) (except the disease is clinically controlled) or acquired immune deficiency syndrome (AIDS).
  14. Patients with any type of primary immunodeficiency or autoimmune disorder requiring treatment.
  15. Major surgery within 4 weeks prior to the first dose of the study drug.
  16. Prior organ allograft transplantations or allogeneic peripheral blood stem cell (PBSC)/bone marrow (BM) transplantation.
  17. Clinically significant cardiac conditions, including myocardial infarction within the last 6 months, uncontrolled angina, viral myocarditis, pericarditis, cerebrovascular accident, or other acute uncontrolled heart disease < 3 months prior to the first dose of the study drug.
  18. Patients with underlying hemoglobinopathies (eg, thalassemia) will be excluded, this criterion only applicable to the ADG106 plus ADG116 combination groups.
  19. Pulmonary embolism or deep vein thrombosis within 3 months prior to the first dose of study drug.
  20. Live viral vaccine therapies within 4 weeks prior to the first dose of study drug.
  21. Any known, documented, or suspected history of illicit substance abuse.
  22. Any other disease or clinically significant abnormality in laboratory parameters, including serious medical or psychiatric illness/condition, which in the judgment of the Investigator might compromise the safety of the patient or integrity of the study, interfere with the patient participation in the trial or compromise the trial objectives

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04501276


Contacts
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Contact: Kristine She 4088389296 kristine_she@adagene.com
Contact: Jiping Zha (650)785-9347 jiping_zha@adagene.com

Locations
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United States, Texas
Next Oncology Recruiting
San Antonio, Texas, United States, 78229
Contact: Anthony Tolcher         
Australia
Ashford Cancer Centre Research Recruiting
Kurralta Park, Australia
Contact: Francis Parnis       fparnis@adelaidecancercentre.com.au   
Cabrini Hospital Recruiting
Malvern, Australia
Contact: Gary Richardson       gary.richardson@ocv.net.au   
Macquarie University Recruiting
Sydney, Australia
Contact: John Park       john.park@mqhealth.org.au   
Sponsors and Collaborators
Adagene Inc
Additional Information:
Publications:

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Responsible Party: Adagene Inc
ClinicalTrials.gov Identifier: NCT04501276    
Other Study ID Numbers: ADG116-1003
First Posted: August 6, 2020    Key Record Dates
Last Update Posted: February 9, 2022
Last Verified: January 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Adagene Inc:
Advanced/Metastatic Solid Tumors
Additional relevant MeSH terms:
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Neoplasms