This is a Phase 1b/2, open-label, dose escalation, dose expansion and dose optimization study to evaluate the safety, tolerability, PK, and immunogenicity of ADG126-pembrolizumab combination regimens in patients with advanced/metastatic solid tumors. The 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).
This is a Phase 1b/2, open-label, multicenter, dose escalation, dose expansion and dose optimization study to evaluate the safety, tolerability, PK, and preliminary efficacy of ADG126-Pembrolizumab or ADG126-Pembrolizumab in combination with trifluridine/tipiracil-bevacizumab or fruquintinib in patients with advanced/metastatic solid tumors, with a focus on MSS CRC. In Phase 2, the study will use a randomized design to evaluate the dose optimization regimen in patients with MSS CRC for ADG126- Pembrolizumab doublet only.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
186
ADG126 is an anti-CTLA-4 fully human monoclonal antibody that specifically binds to human CTLA-4.
Pembrolizumab (KEYTRUDA®) is a PD-1 receptor-blocking antibody (a humanized IgG4 monoclonal antibody).
The standard of care therapies will include Trifluridine/Tipiracil-Bevacizumab, approved for treating metastatic colorectal cancer (CRC)and various solid tumors.
Honor Health Research Institute
Scottsdale, Arizona, United States
Maximum tolerated dose (MTD) and RP2D for ADG126 in combination with pembrolizumab.
To determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) for ADG126+ pembrolizumab in dose escalation levels
Time frame: 9 months
the safety and tolerability of ADG126 at escalating dose level in combination with pembrolizumab in adults with advanced metastatic solid tumors
Incidence rate of AEs as assessed by CTCAE v5.0
Time frame: 9 months
Access the preliminary antitumor activity of ADG126-pembrolizumab combination regimens
Number of Participants with preliminary antitumor activity
Time frame: 9 months
Maximum tolerated dose (MTD) and/or RP2D for ADG126 with Trifluridine/Tipiracil-Bevacizumab
To assess the safety and tolerability of ADG126 + pembrolizumab in combination with the following SOC therapies (Trifluridine/tipiracil-bevacizumab) in MSS CRC To determine the MTD and/or RP2D for ADG126 + pembrolizumab in combination with the following SOC therapies in MSS CRC:
Time frame: 6 months
Access the preliminary antitumor activity of ADG126 with Pembrolizumab in combination standard of care
To assess the preliminary antitumor activity of ADG126 + pembrolizumab in combination with the following SOC therapies in MSS CRC (Trifluridine/tipiracil-bevacizumab) SOC (Fruquintinib)
Time frame: 6 months
Access and characterize the optimal dose based on safety and efficacy parameters
To characterize the optimal dose based on safety and efficacy parameters
Time frame: 9 months
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
The standard of care therapy, Fruquintinib, is approved for treating metastatic colorectal cancer (CRC) and various solid tumors.
City of Hope National Medical Center
Duarte, California, United States
RECRUITINGCity of Hope Orange County
Irvine, California, United States
RECRUITINGFlorida cancer specialist/Sarah Cannon Research Institute
Sarasota, Florida, United States
ACTIVE_NOT_RECRUITINGThe Cleveland Clinic
Cleveland, Ohio, United States
RECRUITINGMD Anderson Cancer Center
Houston, Texas, United States
RECRUITINGFred Hutchinson Cancer Center
Seattle, Washington, United States
RECRUITINGFujian Cancer Hospital
Fuzhou, Fujian, China
RECRUITINGSunYat-Sen University Cancer Center
Guangzhou, Guangdong, China
RECRUITINGHong Kong Humanity & Health Clinical Trial Center
Hong Kong, Hong Kong, China
RECRUITING...and 11 more locations
Pharmacokinetic (PK) profile/parameters
Area under the time concentration curve (AUC) from time zero to infinity (AUC0-inf)
Time frame: 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)
Time frame: 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)
Time frame: From first dose (Cycle 1 Day 1,) until the last dose (up to 2 years)
Trough concentration (Ctrough)
Trough concentration (Ctrough)
Time frame: 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.
Time frame: 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.
Time frame: 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 iRECIST)
Time frame: 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.
Time frame: From first dose (Cycle 1 Day 1,) until the last dose (up to 2 years)
To assess the efficacy outcomes in the defined patient population
The dose optimization arm will be used to access the efficacy outcome derived in the defined patient population
Time frame: From first dose (Cycle 1 Day 1,) until the last dose (up to 2 years)