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NCT05405595PHASE1, PHASE2Recruiting

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

Adagene Inc

Start Date

6/15/2022

Completion Date

4/30/2027

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.

Eligibility Criteria

Age Range: 18 years to No maximum

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.

Interventions

DRUG

ADG126

DRUG

Pembrolizumab (KEYTRUDA®)

DRUG

Standard of Care (Trifluridine/Tipiracil-Bevacizumab)

DRUG

Standard of care (Fruquintinib)

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Conditions

Advanced/Metastatic Solid Tumors

Locations

Honor Health Research Institute

Scottsdale, Arizona 85251

United States

City of Hope National Medical Center

Duarte, California 91010

United States

City of Hope Orange County

Irvine, California 92618

United States

Florida cancer specialist/Sarah Cannon Research Institute

Sarasota, Florida 34232

United States

The Cleveland Clinic

Cleveland, Ohio 44195-0001

United States

MD Anderson Cancer Center

Houston, Texas 77030

United States

Fred Hutchinson Cancer Center

Seattle, Washington 98109

United States

Fujian Cancer Hospital

Fuzhou, Fujian

China

SunYat-Sen University Cancer Center

Guangzhou, Guangdong

China

Hong Kong Humanity & Health Clinical Trial Center

Hong Kong, Hong Kong

China

Prince of Wales Hospital

Hong Kong, Hong Kong

China

Dong -A University Hospital

Seogu, Busan Gwangyeogsi 49201

South Korea

CHA Bundang Medical Center, CHA university

Seongnam, Gyeonggido 13496

South Korea

The Catholic University of Korea Street. Vincent Hospital

Suwon, Gyeonggido 16247

South Korea

Chungbuk National University Hospital

Cheongju-si, North Chungcheong 28644

South Korea

Samsung Medical Center

Seoul, Seoul Teugbyeolsi 06351

South Korea

Keimyung University Dongsan Hospital

Daegu, 41931

South Korea

Seoul National University Hospital

Seoul, 03080

South Korea

KangBuk Samsung Hospital

Seoul, 03081

South Korea

Asan Medical Center

Seoul, 05505

South Korea

Severance Hospital Yonsei University Health System

Seoul, 3722

South Korea