A Phase 1b/2 Study of ADG116, ADG116 Combined With Anti-PD-1 Antibody or Anti-CD137 Antibody in Solid Tumors Patients

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Advanced/Metastatic Solid Tumors

Intervention / Treatment
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* Drug: ADG116
* Drug: ADG106
* Drug: anti PD1 drug


Participation Criteria
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Eligibility Criteria
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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. Patients with advanced or metastatic solid tumors, who have progressed after all standard therapies, or for whom no further standard therapy exists. At least 1 measurable lesion at baseline according to the definition of RECIST v1.1. Adequate organ function. Exclusion Criteria: • Patients who meet any of the following criteria cannot be enrolled: Pregnant or breastfeeding females. Childbearing potential who does not agree to the use of contraception during the treatment period.. Treatment with any investigational drug within washout period. Grade ≥ 3 immune-related AEs (irAEs) or irAE that lead to discontinuation of prior immunotherapy. Central nervous system disease involvement History or risk of autoimmune disease. 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 requiring systemic treatment with corticosteroids Patients receiving granulocyte colony stimulating factor (G-CSF), within 14 days prior to the first dose of the study drug. Any uncontrolled active infections requiring systemic antimicrobial treatment (viral, bacterial, or other), or uncontrolled or poorly controlled, asthma, chronic obstructive pulmonary disease (COPD). Major surgery within 4 weeks prior to the first dose of the study drug. Has had an allogeneic tissue/solid organ transplant.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part A : Dose escalation of ADG116 monotherapy<br> | Drug: ADG116<br>* 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.<br>|
| Experimental: Part B : Dose escalation of ADG116 combined with anti PD1 drug<br> | Drug: ADG116<br>* 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.<br>Drug: anti PD1 drug<br>* 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.<br>|
| Experimental: Part C : Dose escalation of ADG116 combined with ADG106<br> | Drug: ADG116<br>* 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.<br>Drug: ADG106<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants experiencing dose-limiting toxicities escalating dose levels in adults with advanced / metastatic solid tumors |  | From first dose of ADG116 (Week 1 Day 1) until 21 days | 
| Number of participants with adverse events as assessed by CTCAE v5.0 |  | From first dose of ADG116 (Week 1 Day 1) to 28 days post last dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the time concentration curve (AUC) from time zero to infinity (AUC0-inf) |  | From first dose (Cycle 1 Day 1, ) until the last dose (up to 2 years) | 
| Maximum (peak) plasma concentration (Cmax) |  | From first dose (Cycle 1 Day 1,) until the last dose (up to 2 years) | 
| Time to maximum (peak) plasma concentration (Tmax) |  | From first dose (Cycle 1 Day 1,) until the last dose (up to 2 years) | 
| Trough plasma concentration (Ctrough) |  | From first dose (Cycle 1 Day 1,) until the last dose (up to 2 years) | 
| Incidence of ADAs |  | From first dose (Cycle 1 Day 1,) until the last dose (up to 2 years) | 
| 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). |  | From first dose of ADG116 (Week 1 Day 1) to 28 days post last dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Advanced/Metastatic Solid Tumors