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
Summary
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).
Detailed description
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.
Arms & interventions
- DrugADG126
ADG126 is an anti-CTLA-4 fully human monoclonal antibody that specifically binds to human CTLA-4.
- DrugPembrolizumab (KEYTRUDA®)
Pembrolizumab (KEYTRUDA®) is a PD-1 receptor-blocking antibody (a humanized IgG4 monoclonal antibody).
- DrugStandard of Care (Trifluridine/Tipiracil-Bevacizumab)
The standard of care therapies will include Trifluridine/Tipiracil-Bevacizumab, approved for treating metastatic colorectal cancer (CRC)and various solid tumors.
- DrugStandard of care (Fruquintinib)
The standard of care therapy, Fruquintinib, is approved for treating metastatic colorectal cancer (CRC) and various solid tumors.
Outcome measures
Primary
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
Secondary
Pharmacokinetic (PK) profile/parameters
Time frame: From first dose (Cycle 1 Day 1,) until the last dose (up to 2 years)
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 frame: From first dose (Cycle 1 Day 1,) until the last dose (up to 2 years)
Trough concentration (Ctrough)
Time frame: From first dose (Cycle 1 Day 1,) until the last dose (up to 2 years)
Incidence of ADAs
Time frame: From first dose (Cycle 1 Day 1,) until the last dose (up to 2 years)
To assess the disease control rate (DCR)
Time frame: From first dose (Cycle 1 Day 1,) until the last dose (up to 2 years)
To assess the progression free survival (PFS)
Time frame: From first dose (Cycle 1 Day 1,) until the last dose (up to 2 years)
To assess the overall survival (OS)
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
Time frame: From first dose (Cycle 1 Day 1,) until the last dose (up to 2 years)
Eligibility criteria
Study locations (7)
Honor Health Research Institute
Scottsdale, Arizona, 85251
City of Hope National Medical Center
Duarte, California, 91010
City of Hope Orange County
Irvine, California, 92618
Florida cancer specialist/Sarah Cannon Research Institute
Sarasota, Florida, 34232
The Cleveland Clinic
Cleveland, Ohio, 44195-0001
MD Anderson Cancer Center
Houston, Texas, 77030
Fred Hutchinson Cancer Center
Seattle, Washington, 98109