ADG126, ADG126 in Combination With Anti PD1 Antibody, and ADG126 in Combination With ADG106 in Advanced/Metastatic Solid Tumors

Study Overview
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Brief Summary
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ADG126, ADG126 in Combination with anti-PD1 antibody, and ADG126 in Combination with ADG106 in Patients with Advanced/Metastatic Solid Tumors .

Detailed Description
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ADG126 is a novel anti-CTLA-4 fully human IgG1 antibody prodrug that is modified with Adagene Safebody technology to control the activation of anti-CTLA4 activity.ADG106 is a fully human ligand-blocking, agonistic anti-CD137 IgG4 mAb which is expected to enhance the activity of activated T cells. The enhanced antitumor efficacy results observed from the preclinical studies of ADG126 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 First-in-Human (FIH), Open-Label, Phase 1/2 Dose Escalation and Expansion Study of ADG126, ADG126 in Combination With Anti PD1 Antibody, and ADG126 in Combination With ADG106 in Patients With Advanced/Metastatic Solid Tumors

Conditions
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Advanced/Metastatic Solid Tumors

Intervention / Treatment
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* Biological: ADG126 Mono
* Biological: ADG126-anti PD1
* Biological: ADG126-ADG106


Participation Criteria
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Eligibility Criteria
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Inclusion criteria Adults ≥18 years of age. ECOG performance status 0 or 1. Estimated life expectancy of more than 12 weeks . Patients with advanced or metastatic solid tumors, confirmed by histologically or pathologically documented, 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. Meets the additional tumor type requirements as specified in Protocol. Exclusion Criteria: Treatment with any investigational drug within washout period. Major trauma or major surgery within 4 weeks prior to first dose of study drug(s) History of significant immune-mediated AE. Central nervous system (CNS) disease involvement. Prior organ allograft transplantations or allogeneic peripheral blood stem cell (PBSC)/bone marrow (BM) transplantation Clinically significant cardiac disease. Evidence of active uncontrolled viral, bacterial, or systemic fungal infection. Patients who received: A COVID-19 vaccine within 7 days of Cycle 1 Day 1. Live vaccines or live-attenuated vaccines within 28 days prior to Cycle 1 Day 1. Known active infection of HBV/BCV/HIV. Patients requiring systemic treatment with corticosteroids or other immunosuppressive medications (>10 mg/day prednisone or equivalent). Second primary malignancy not in remission for greater than 3 years. History(within the last 5 years) or risk of autoimmune disease. Pregnant or breastfeeding females. Childbearing potential who does not agree to the use of contraception during the treatment period.

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: ADG126 mono dose escalation<br>ADG126 monotherapy dose escalation will be traditional 3+3 cohort design. | Biological: ADG126 Mono<br>* ADG126 will be administered as an IV infusion over 30-60 minutes ± 15 minutes.<br>|
| Experimental: ADG126 mono dose expansion<br>Monotherapy dose expansion is designed to evaluate the preliminary antitumor activity of ADG126 at RP2D or the doses approved by the SRC. | Biological: ADG126 Mono<br>* ADG126 will be administered as an IV infusion over 30-60 minutes ± 15 minutes.<br>|
| Experimental: ADG126-anti PD1 drug dose escalation<br>Combination therapy will commence at a dose level lower than the cleared dose from the monotherapy dose escalation arms and approved by the SRC. | Biological: ADG126-anti PD1<br>* ADG126-toripalimab combination regimen will receive of toripalimab 15 to 30 minutes after the end of the ADG126 infusion<br>|
| Experimental: ADG126-anti PD1 drug dose expansion<br>Combination therapy expansion will commence at RP2D or the dose approved by the SRC. | Biological: ADG126-anti PD1<br>* ADG126-toripalimab combination regimen will receive of toripalimab 15 to 30 minutes after the end of the ADG126 infusion<br>|
| Experimental: ADG126-ADG106 dose escalation<br>Combination therapy will commence at a dose level lower than the cleared dose from the monotherapy dose escalation arms and approved by the SRC. | Biological: ADG126-ADG106<br>* ADG126-ADG106 combination regimen will be receive of ADG106 15 to 30 minutes after the end of the ADG126 infusion<br>|
| Experimental: ADG126-ADG106 dose expansion<br>Combination therapy expansion will commence at RP2D or the dose approved by the SRC. | Biological: ADG126-ADG106<br>* ADG126-ADG106 combination regimen will be receive of ADG106 15 to 30 minutes after the end of the ADG126 infusion<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 ADG126 (Week 1 Day 1) until 21 days | 
| Number of participants with adverse events as assessed by CTCAE v5.0 ADG126-ADG106 combination regimens |  | From first dose of ADG126 (Week 1 Day 1) to 90 days post last dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Antidrug antibodies (ADAs) |  | 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) |  | 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) | 

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