ADG126 in Combination With Pembrolizumab in Patients With Advanced/Metastatic Solid Tumors
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
2 other identifiers
interventional
186
3 countries
21
Brief 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).
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Jun 2022
Longer than P75 for phase_1
21 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
May 16, 2022
CompletedFirst Posted
Study publicly available on registry
June 6, 2022
CompletedStudy Start
First participant enrolled
June 15, 2022
CompletedPrimary Completion
Last participant's last visit for primary outcome
October 31, 2026
ExpectedStudy Completion
Last participant's last visit for all outcomes
April 30, 2027
January 7, 2026
January 1, 2026
4.4 years
May 16, 2022
January 6, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (6)
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
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
9 months
Access the preliminary antitumor activity of ADG126-pembrolizumab combination regimens
Number of Participants with preliminary antitumor activity
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:
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)
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
9 months
Secondary Outcomes (9)
Pharmacokinetic (PK) profile/parameters
From first dose (Cycle 1 Day 1,) until the last dose (up to 2 years)
Maximum (peak) plasma concentration (Cmax)
From first dose (Cycle 1 Day 1,) until the last dose (up to 2 years)
Time to maximum (peak) concentration (Tmax)
From first dose (Cycle 1 Day 1,) until the last dose (up to 2 years)
Trough concentration (Ctrough)
From first dose (Cycle 1 Day 1,) until the last dose (up to 2 years)
Incidence of ADAs
From first dose (Cycle 1 Day 1,) until the last dose (up to 2 years)
- +4 more secondary outcomes
Study Arms (4)
ADG126 in combination with Pembrolizumab (Trade name KEYTRUDA®)
EXPERIMENTALAn IV infusion of ADG126 over 60-90 minutes will be administered 30-60 minutes after administration of pembrolizumab (KEYTRUDA®) infusion. A treatment cycle will consist of 21 days. ADG126 and Pembrolizumab (KEYTRUDA®) combination treatment both will be dosed until progressive disease (PD), intolerable toxicities, withdrawals of consent, or up to 35 cycles.
ADG126 and pembrolizumab (KEYTRUDA®) in combination with Trifluridine/Tipiracil-Bevacizumab
EXPERIMENTALTo evaluate the preliminary antitumor efficacy of ADG126 and Pembrolizumab (KEYTRUDA®) in combination with SOC (Trifluridine/Tipiracil-Bevacizumab) while assessing safety and tolerability. Standard of care treatment will be administered according to the specifications outlined in the Investigational Brochure. Will be dosed until progressive disease (PD), intolerable toxicities, withdrawals of consent, or up to 35 cycles.
ADG126 and pembrolizumab (KEYTRUDA®) in combination with fruquintinib
EXPERIMENTALTo evaluate the preliminary antitumor efficacy of ADG126 and Pembrolizumab (KEYTRUDA®) in combination with SOC (Fruquintinib) while assessing safety and tolerability. The dose strength for treatment will be based on the IB and protocol. Fruquintinib (Fruzaqla) is orally given once daily for the first 21 days of each 28-day cycle. Each treatment cycle consists of 14 days. Will be dosed until progressive disease (PD), intolerable toxicities, withdrawals of consent, or up to 35 cycles.
Dose Optimization
EXPERIMENTALThe randomized phase 2 Dose Optimization arm is intended to test two dosing regimens of ADG126 in combination with pembrolizumab (KEYTRUDA®), which allows the selection of an optimal regimen. The study treatments may continue for up to 35 treatments for pembrolizumab (KEYTRUDA®) if given every 21 days and 18 treatments for pembrolizumab (KEYTRUDA®) if given every 42 days until PD, intolerable toxicities or withdrawal of consent.
Interventions
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.
The standard of care therapy, Fruquintinib, is approved for treating metastatic colorectal cancer (CRC) and various solid tumors.
Eligibility Criteria
You may qualify if:
- ≥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.
You may not qualify if:
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Adagene Inclead
- Merck Sharp & Dohme LLCcollaborator
Study Sites (21)
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
MeSH Terms
Interventions
Intervention Hierarchy (Ancestors)
Study Officials
- STUDY DIRECTOR
Jiping Zha, MD, PhD
Adagene Inc
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
May 16, 2022
First Posted
June 6, 2022
Study Start
June 15, 2022
Primary Completion (Estimated)
October 31, 2026
Study Completion (Estimated)
April 30, 2027
Last Updated
January 7, 2026
Record last verified: 2026-01
Data Sharing
- IPD Sharing
- Will not share