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

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

Detailed Description
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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 ADG 126- Pembrolizumab combination regimens 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).

Official Title
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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

Conditions
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Advanced/Metastatic Solid Tumors

Intervention / Treatment
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* Drug: ADG126


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ≥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. An archival tumor biopsy is required and should be taken within 2 years of enrollment. If not available, a fresh tumor biopsy is acceptable. Exclusion Criteria: 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. Prior treatment with an anti-CTLA-4 therapy. History of significant immune-mediated AE. Central nervous system (CNS) disease involvement. History or risk of autoimmune disease. Patients requiring systemic treatment with corticosteroids or other immunosuppressive medications (>10 mg/day prednisone or equivalent). 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. 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. A positive COVID-19 test within 14 days of Cycle 1 Day 1.

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
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ADG126 in combination with Pembrolizumab<br>An IV infusion of ADG126 over 60-90 minutes will be administered 30-60 minutes after administration of pembrolizumab infusion. A treatment cycle will consist of 21 days. | Drug: ADG126<br>* ADG126 and Pembrolizumab combination treatment both will be dosed until progressive disease (PD), intolerable toxicities, withdrawals of consent, or up to 35 cycles.<br>* Other names: Pembrolizumab;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum tolerated dose (MTD) and RP2D for ADG126 in combination with pembrolizumab. | Number of participants experiencing maximum tolerated dose (MTD) in dose escalation levels in adults with advanced/metastatic solid tumor | 9 months | 
| the safety and tolerability of ADG126 in combination with pembrolizumab | Number of participants with adverse events as assessed by CTCAE v5.0 | 9 months | 
| Access the preliminary antitumor activity of ADG126-pembrolizumab combination regimens | Number of Participants with preliminary antitumor activity | 9 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic (PK) profile/parameters | 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) | Maximum (peak) plasma concentration (Cmax) | From first dose (Cycle 1 Day 1,) until the last dose (up to 2 years) | 
| Time to maximum (peak) concentration (Tmax) | Time to maximum (peak) concentration (Tmax) | From first dose (Cycle 1 Day 1,) until the last dose (up to 2 years) | 
| Trough concentration (Ctrough) | Trough concentration (Ctrough) | From first dose (Cycle 1 Day 1,) until the last dose (up to 2 years) | 
| Incidence of ADAs | this will be summarized for all patients who received at least 1 administration of ADG126. efficacy and safety will be evaluated. | From first dose (Cycle 1 Day 1,) until the last dose (up to 2 years) | 
| To assess the disease control rate (DCR) | this will be calculated as the proportion/percentage of patients with best overall response of CR,PR,SD or progressive disease will be calculated. | From first dose (Cycle 1 Day 1,) until the last dose (up to 2 years) | 
| To assess the progression free survival (PFS) | PFS will be censored at the time of the last evaluable tumor assessment (RECISTv1.1 and /or iRECIST) | From first dose (Cycle 1 Day 1,) until the last dose (up to 2 years) | 
| To assess the overall survival (OS) | this will be used to estimate median survival times where applicable. | From first dose (Cycle 1 Day 1,) until the last dose (up to 2 years) |