ADG116 + Immunotherapy for Cancer

Recruiting at 4 trial locations

Overseen By Jiping Zha

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Adagene Inc

Must not be taking: Corticosteroids, G-CSF

Disqualifiers: Pregnancy, Autoimmune disease, CNS disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

72 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Eligibility Criteria

Adults over 18 with advanced solid tumors who've exhausted standard treatments or can't access them may join this trial. They should have a life expectancy over 12 weeks, be relatively healthy (ECOG status 0-1), and have at least one measurable tumor lesion. Prior therapies must be completed at least 4 weeks before the study starts, and they shouldn't have severe previous side effects from similar drugs.

Inclusion Criteria

Patients must meet all of the following inclusion criteria to be eligible for participation in this study: ≥ 18 years of age at the time of informed consent. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 with no deterioration over the previous 2 weeks. Estimated life expectancy of more than 12 weeks. 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. 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. Adequate hematologic function, defined by the following: 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. 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. Hemoglobin ≥ 9 g/dL without transfusion or erythropoietin within 2 weeks (≤ 14 days) prior to study treatment. 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. Adequate renal function defined by either a creatinine clearance ≥ 60 mL/min (by Cockcroft-Gault formula) or serum creatinine (SCr) < 1.5 × ULN Coagulation tests, defined by the following: Activated partial thromboplastin time (aPTT) ≤ 1.5 × ULN. International normalized ratio (INR) ≤ 1.5 × ULN. Exception: INR 2 to ≤ 3 × ULN is acceptable for patients on Warfarin anticoagulation. Left ventricular ejection fraction (LVEF) ≥ 50% measured by multiple-gated acquisition (MUGA) or echocardiogram. 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. 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: Pregnant or breastfeeding females. 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. Treatment with any investigational drug within 4 weeks prior to the first dose of study drug. Grade ≥ 3 immune-related AEs (irAEs) or irAE that lead to discontinuation of prior immunotherapy. 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. 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. 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. 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. Peripheral neuropathy Grade ≥ 2. 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. 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. 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. Known positive test result for human immunodeficiency virus (HIV) (except the disease is clinically controlled) or acquired immune deficiency syndrome (AIDS). Patients with any type of primary immunodeficiency or autoimmune disorder requiring treatment. Major surgery within 4 weeks prior to the first dose of the study drug. Prior organ allograft transplantations or allogeneic peripheral blood stem cell (PBSC)/bone marrow (BM) transplantation. 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. Patients with underlying hemoglobinopathies (eg, thalassemia) will be excluded, this criterion only applicable to the ADG106 plus ADG116 combination groups. Pulmonary embolism or deep vein thrombosis within 3 months prior to the first dose of study drug. Live viral vaccine therapies within 4 weeks prior to the first dose of study drug. Any known, documented, or suspected history of illicit substance abuse. 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

Treatment Details

Interventions

• ADG106
• ADG116
• Anti-PD-1 Antibody

Trial Overview The trial is testing ADG116, an antibody targeting CTLA-4, which might help the immune system fight cancer. It's also looking at combining ADG116 with either ADG106 or an anti-PD-1 drug to see if these combinations are more effective in treating solid tumors than each drug alone.

Participant Groups

Group I: Part C : Dose escalation of ADG116 combined with ADG106 Experimental Treatment 2 Interventions

Group II: Part B : Dose escalation of ADG116 combined with anti PD1 drug Experimental Treatment 2 Interventions

Group III: Part A : Dose escalation of ADG116 monotherapy Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

Adagene Inc

Lead Sponsor

Trials

12

Recruited

1,000+