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ADG126 in Combination With Pembrolizumab in Patients With Advanced/Metastatic Solid Tumors

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05405595
Recruitment Status : Recruiting
First Posted : June 6, 2022
Last Update Posted : July 25, 2022
Sponsor:
Collaborator:
Merck Sharp & Dohme LLC
Information provided by (Responsible Party):
Adagene Inc

Brief Summary:
This is a Phase 1b/2, open-label, dose escalation study to evaluate the safety, tolerability, PK, and immunogenicity of an ADG126-pembrolizumab combination regimen in patients with advanced/metastatic solid tumors.

Condition or disease Intervention/treatment Phase
Advanced/Metastatic Solid Tumors Drug: ADG126 Phase 1

Detailed Description:

This is a Phase 1b/2, open label, multicenter, dose escalation and dose expansion study to evaluate the safety, tolerability, PK, and preliminary efficacy of an ADG126-pembrolizumab combination regimen in patients with advanced/metastatic solid tumors.

Study drug ADG126 is an anti -CTLA-4 fully human monoclonal antibody that specifically binds to human CTLA-4. Pembrolizumab is a PD-1 receptor-blocking antibody (a humanized IgG4 monoclonal antibody).

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 102 participants
Allocation: N/A
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1b/2, Open-Label, Dose Escalation and Expansion Study of ADG126 in Combination With Pembrolizumab (Anti PD-1 Antibody) in Patients With Advanced/Metastatic Solid Tumors
Actual Study Start Date : June 15, 2022
Estimated Primary Completion Date : March 30, 2025
Estimated Study Completion Date : September 30, 2025

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: ADG126 in combination with Pembrolizumab
IV infusion of ADG126 over 60-90 minutes will be administered 30-60 minutes post administration of Pembrolizumab. Cycles is 21 days with ADG126 and Pembrolizumab being administered on each day of treatment cycle. DLT will be evaluated during the initial 21days.
Drug: ADG126
ADG126 and pembrolizumab will be administered using IV infusion on Day 1 of each treatment cycle after all procedures and assessments have been completed.
Other Name: Pembrolizumab




Primary Outcome Measures :
  1. Dose-limiting toxicity (DLT) and RP2D for ADG126 in combination with pembrolizumab. [ Time Frame: 9 months ]
    Number of participants experiencing dose-limiting toxicities escalating dose levels in adults with advanced / metastatic solid tumor

  2. the safety and tolerability of ADG126 in combination with pembrolizumab [ Time Frame: 9 months ]
    Number of participants with adverse events as assessed by CTCAE v5.0

  3. the maximum tolerated dose (MTD) for ADG126 in combination with pembrolizumab. [ Time Frame: 9 months ]
  4. recommended Phase 2 dose (RP2D) of ADG126 in combination with pembrolizumab [ Time Frame: 9 months ]

Secondary Outcome Measures :
  1. Pharmacokinetic (PK) profile/parameters [ Time Frame: From first dose (Cycle 1 Day 1,) until the last dose (up to 2 years) ]
    Area under the time concentration curve (AUC) from time zero to infinity (AUC0-inf)

  2. Maximum (peak) plasma concentration (Cmax) [ Time Frame: From first dose (Cycle 1 Day 1,) until the last dose (up to 2 years) ]
    Maximum (peak) plasma concentration (Cmax)

  3. Time to maximum (peak) concentration (Tmax) [ Time Frame: From first dose (Cycle 1 Day 1,) until the last dose (up to 2 years) ]
    Time to maximum (peak) concentration (Tmax)

  4. Trough concentration (Ctrough) [ Time Frame: From first dose (Cycle 1 Day 1,) until the last dose (up to 2 years) ]
    Trough concentration (Ctrough)

  5. Incidence of ADAs [ Time Frame: From first dose (Cycle 1 Day 1,) until the last dose (up to 2 years) ]
    this will be summarized for all patients who received at least 1 administration of Adg126. efficacy and safety will be evaluated.

  6. To assess the disease control rate (DCR) [ Time Frame: From first dose (Cycle 1 Day 1,) until the last dose (up to 2 years) ]
    this will be calculated as the proportion/percentage of patients with best overall response of CR,PR,SD or progressive disease will be calculated.

  7. To assess the progression free survival (PFS) [ Time Frame: From first dose (Cycle 1 Day 1,) until the last dose (up to 2 years) ]
    PFS will be censored at the time of the last evaluable tumor assessment (RECISTv1.1 and /or iRECIST)

  8. To assess the overall survival (OS) [ Time Frame: From first dose (Cycle 1 Day 1,) until the last dose (up to 2 years) ]
    this will be used to estimate median survival times where applicable.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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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:

  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. Patients with advanced or metastatic solid tumors, histologically or pathologically confirmed, 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.
  4. Patients should have at least 1 measurable lesion at baseline according to the definition of RECIST v1.1. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
  5. 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 ≥ 75 × 109/L without transfusion within 2 weeks (≤ 14 days) prior to study treatment.
    3. Hemoglobin ≥ 8 g/dL without transfusion or erythropoietin within 2 weeks (≤ 14 days) prior to study treatment.
  6. AST and ALT ≤ 2.5 × 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 may be enrolled. Patients with known liver metastases or patients with hepatocellular carcinoma may be enrolled with AST, ALT and/or total bilirubin ≤ 5 × the ULN
  7. Adequate renal function defined by either a creatinine clearance ≥ 45 mL/min (by Cockcroft-Gault formula) or SCr ≤ 1.5 × ULN.
  8. Coagulation tests, defined by the following:

    1. aPTT ≤ 1.5 × ULN.
    2. INR ≤ 1.5 × ULN. Exception: INR ≤ 3 × ULN is acceptable for patients on Warfarin anticoagulation.
  9. Previous AEs have been improved to baseline or Grade ≤ 1 NCI CTCAE v5.0 (except for patients with alopecia). Participants with Grade ≤ 2 neuropathy may be eligible. Participants with endocrine-related AEs Grade ≤ 2 requiring treatment or hormone replacement may be eligible.

Exclusion Criteria:

  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 6 months 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 led to discontinuation of prior immunotherapy.
  5. Has known active CNS metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, i.e., without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study treatment.
  6. Has an active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed.
  7. Active viral (any etiology) hepatitis patients are excluded. Hepatitis B virus (HBV) carriers are ineligible. Cured Hepatitis C virus (HCV) (negative HCV RNA test) patients may be enrolled after consulting with the Medical Monitor.
  8. 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 ≥ 8, asthma, COPD, or other conditions that pose a risk to the patient participating on study.
  9. Has a known history of HIV infection.
  10. Patients with any type of primary immunodeficiency or autoimmune disorder requiring treatment.
  11. Major surgery within 4 weeks prior to the first dose of the study drug.
  12. Has had an allogeneic tissue/solid organ transplant.
  13. 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; left ventricular ejection fraction (LVEF) < 50%, New York Heart Association (NYHA) Class III or IV congestive heart failure, or uncontrolled hypertension.
  14. Pulmonary embolism or deep vein thrombosis within 3 months prior to the first dose of study drug.
  15. Has received a COVID-19 vaccine within 7 days prior to the first dose of study treatment. Has received a live or live-attenuated vaccine within 30 days prior to the first dose of study treatment. Note: Administration of killed vaccines are allowed.
  16. A positive COVID-19 test within 14 days of Cycle 1 Day 1.
  17. 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): NCT05405595


Contacts
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Contact: Kristine She, MS 404-838-9296 kristine_she@adagene.com
Contact: Jiping Zha, MD 650-358-9002 jiping_zha@adagene.com

Locations
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United States, Arizona
HonorHealth Research Institute Recruiting
Scottsdale, Arizona, United States, 85251
Contact: Sharma Sunil, MD         
United States, California
City of Hope National Medical Center Not yet recruiting
Duarte, California, United States, 91010
Contact: Daneng Li, MD         
Sponsors and Collaborators
Adagene Inc
Merck Sharp & Dohme LLC
Investigators
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Study Chair: Jiping zha, MD Adagene Inc
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Responsible Party: Adagene Inc
ClinicalTrials.gov Identifier: NCT05405595    
Other Study ID Numbers: ADG126-P001
KEYNOTE-C98 ( Other Identifier: Merck )
First Posted: June 6, 2022    Key Record Dates
Last Update Posted: July 25, 2022
Last Verified: July 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
Additional relevant MeSH terms:
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Neoplasms
Pembrolizumab
Antineoplastic Agents, Immunological
Antineoplastic Agents