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

Official title

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

Overview

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.

Interventions

• Drug ADG126
  ADG126 is an anti-CTLA-4 fully human monoclonal antibody that specifically binds to human CTLA-4.
• Drug Pembrolizumab (KEYTRUDA®)
  Pembrolizumab (KEYTRUDA®) is a PD-1 receptor-blocking antibody (a humanized IgG4 monoclonal antibody).
• Drug Standard 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.
• Drug Standard of care (Fruquintinib)
  The standard of care therapy, Fruquintinib, is approved for treating metastatic colorectal cancer (CRC) and various solid tumors.

Primary outcome measures

• Maximum tolerated dose (MTD) and RP2D for ADG126 in combination with pembrolizumab. [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 [Time frame: 9 months]
• Access the preliminary antitumor activity of ADG126-pembrolizumab combination regimens [Time frame: 9 months]
• Maximum tolerated dose (MTD) and/or RP2D for ADG126 with Trifluridine/Tipiracil-Bevacizumab [Time frame: 6 months]
• Access the preliminary antitumor activity of ADG126 with Pembrolizumab in combination standard of care [Time frame: 6 months]
• Access and characterize the optimal dose based on safety and efficacy parameters [Time frame: 9 months]

Secondary outcome measures (9)

• 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

Inclusion criteria

• ≥18 years of age at the time of informed consent.
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
• Wash out period from previous antitumor therapies
• 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.
• 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.
• Dose Expansion Phase Only: Tumor tissues (archived tissue) before treatment are required for all patients.

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 a PD-1, PD-L1 targeting agent or a next-generation anti-CTLA-4 therapy with enhanced ADCC function.
• History of significant irAEs or irAE.
• 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.
• History of Hypersensitivity or known to be allergic to protein drugs or recombinant protein.
• Active hemoptysis or central airway invasion by metastatic tumor.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Sequential

Masking

Open label

Primary purpose

Treatment

Study locations

South Korea · 10 centers

• Dong -A University Hospital — Seogu
• CHA Bundang Medical Center, CHA university — Seongnam
• The Catholic University of Korea Street. Vincent Hospital — Suwon
• Chungbuk National University Hospital — Cheongju-si
• Samsung Medical Center — Seoul
• Keimyung University Dongsan Hospital — Daegu
• Seoul National University Hospital — Seoul
• KangBuk Samsung Hospital — Seoul
• … and 2 more centers

United States · 7 centers

• Honor Health Research Institute — Scottsdale
• City of Hope National Medical Center — Duarte
• City of Hope Orange County — Irvine
• Florida cancer specialist/Sarah Cannon Research Institute — Sarasota
• The Cleveland Clinic — Cleveland
• MD Anderson Cancer Center — Houston
• Fred Hutchinson Cancer Center — Seattle

China · 4 centers

• Fujian Cancer Hospital — Fuzhou
• SunYat-Sen University Cancer Center — Guangzhou
• Hong Kong Humanity & Health Clinical Trial Center — Hong Kong
• Prince of Wales Hospital — Hong Kong

Identifiers

NCT: NCT05405595 · ADG126-P001 · KEYNOTE-C98, MK-3475-C98

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗