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RecruitingInterventionalPhase 1/Phase 2

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

NCT ID: NCT05405595Sponsor: Adagene IncLast updated: 2026-01-07

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

Sex: AllAge: 18 Years and olderHealthy volunteers: No
Inclusion Criteria: 1. ≥18 years of age at the time of informed consent. 2. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1. 3. Wash out period from previous antitumor therapies 4. At least 1 measurable lesion at baseline according to the definition of RECIST v1.1. 5. Adequate organ function. 6. An archival tumor biopsy is required and should be taken within 2 years of enrollment. If not available, a fresh tumor biopsy is acceptable. 7. For Dose Escalation Phase Only: Patients with histologically or cytologically confirmed, locally advanced or metastatic solid tumors, who have progressed after all standard therapies, or for whom no further standard therapy exists. 8. Dose Expansion Phase Only: Tumor tissues (archived tissue) before treatment are required for all patients. Exclusion Criteria: 1. Pregnant or breastfeeding females. 2. Childbearing potential who does not agree to the use of contraception during the treatment period. 3. Treatment with any investigational drug within washout period. 4. Prior treatment with a PD-1, PD-L1 targeting agent or a next-generation anti-CTLA-4 therapy with enhanced ADCC function. 5. History of significant irAEs or irAE. 6. Central nervous system (CNS) disease involvement. 7. History or risk of autoimmune disease. 8. Patients requiring systemic treatment with corticosteroids or other immunosuppressive medications (\>10 mg/day prednisone or equivalent). 9. Any uncontrolled active infections requiring systemic antimicrobial treatment (viral, bacterial, or other), or uncontrolled or poorly controlled, asthma, chronic obstructive pulmonary disease (COPD). 10. Major surgery within 4 weeks prior to the first dose of the study drug. 11. Has had an allogeneic tissue/solid organ transplant. 12. 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. 13. A positive COVID-19 test within 14 days of Cycle 1 Day 1. 14. History of Hypersensitivity or known to be allergic to protein drugs or recombinant protein. 15. Active hemoptysis or central airway invasion by metastatic tumor.

Study locations (7)

Honor Health Research Institute

Scottsdale, Arizona, 85251

Recruiting
Sharma Sunil, MD · Contact

City of Hope National Medical Center

Duarte, California, 91010

Recruiting
Daneng Li, MD · Contact
Marwan Fakih, MD · Contact

City of Hope Orange County

Irvine, California, 92618

Recruiting
Pashtoon Kasi, MD · Contact

Florida cancer specialist/Sarah Cannon Research Institute

Sarasota, Florida, 34232

Active Not Recruiting

The Cleveland Clinic

Cleveland, Ohio, 44195-0001

Recruiting
Smitha Krishnamurthi, MD · Contact

MD Anderson Cancer Center

Houston, Texas, 77030

Recruiting
David Hong, MD · Contact
Mary Trahan · Contact

Fred Hutchinson Cancer Center

Seattle, Washington, 98109

Recruiting
Rachael Safyan, MD · Contact