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

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).

Study Overview

• Status: Recruiting
• Conditions: Advanced/Metastatic Solid Tumors
• Intervention / Treatment: Drug: ADG126; Drug: Pembrolizumab (KEYTRUDA®); Drug: Standard of Care (Trifluridine/Tipiracil-Bevacizumab); Drug: Standard of care (Fruquintinib)

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.

• Study Type: Interventional
• Enrollment (Estimated): 186
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Jiping Zha, MD, PhD; Phone Number: 650-785-9347; Email: jiping_zha@adagene.com
• Study Contact Backup: Name: Xiaohong She, MS; Phone Number: 408-838-9296; Email: kristine_she@adagene.com

Study Locations

• China
  • Fujian
    • Fuzhou, Fujian, China
      • Recruiting
      • Fujian Cancer Hospital
      • Contact: Yu Chen, MD
  • Guangdong
    • Guangzhou, Guangdong, China
      • Recruiting
      • SunYat-sen University Cancer Center
      • Contact: Ruihua Xu, MD
  • Hong Kong
    • Hong Kong, Hong Kong, China
      • Recruiting
      • Prince of Wales Hospital
      • Contact: Brigette B.Y Ma, MD
    • Hong Kong, Hong Kong, China
      • Recruiting
      • Hong Kong Humanity & Health Clinical Trial Center
      • Contact: George Lau, MD
• South Korea
  • Daegu, South Korea, 41931
    • Terminated
    • Keimyung University Dongsan Hospital
  • Seoul, South Korea, 05505
    • Recruiting
    • Asan Medical Center
    • Contact: Sun Young Kim, MD
    • Contact: Ko Eun- Young
  • Seoul, South Korea, 03080
    • Recruiting
    • Seoul National University Hospital
    • Contact: Seock -Ah Im, MD
    • Contact: Sae Won Han, MD
  • Seoul, South Korea, 3722
    • Recruiting
    • Severance Hospital Yonsei University Health System
    • Contact: Sang Joon Shin, MD
    • Contact: Da Seul Lee
  • Seoul, South Korea, 03081
    • Terminated
    • Kangbuk Samsung Hospital
  • Busan Gwangyeogsi
    • Seogu, Busan Gwangyeogsi, South Korea, 49201
      • Terminated
      • Dong -A University Hospital
  • Gyeonggido
    • Seongnam, Gyeonggido, South Korea, 13496
      • Recruiting
      • Cha Bundang Medical Center, Cha University
      • Contact: Hing Jae Chon, MD
      • Contact: Song I Kang
    • Suwon, Gyeonggido, South Korea, 16247
      • Terminated
      • The Catholic University of Korea Street. Vincent Hospital
  • North Chungcheong
    • Cheongju-si, North Chungcheong, South Korea, 28644
      • Recruiting
      • Chungbuk National University Hospital
      • Contact: Ki Hyeong Lee, MD
      • Contact: Hee Kyung Kim, MD
  • Seoul Teugbyeolsi
    • Seoul, Seoul Teugbyeolsi, South Korea, 06351
      • Recruiting
      • Samsung Medical Center
      • Contact: Byoung Yong Shim, MD
      • Contact: Jee Yun Lee, MD
• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85251
      • Recruiting
      • Honor Health Research Institute
      • Contact: Sharma Sunil, MD
  • California
    • Duarte, California, United States, 91010
      • Recruiting
      • City of Hope National Medical Center
      • Contact: Daneng Li, MD
      • Contact: Marwan Fakih, MD
    • Irvine, California, United States, 92618
      • Recruiting
      • City of Hope Orange County
      • Contact: Pashtoon Kasi, MD
  • Florida
    • Sarasota, Florida, United States, 34232
      • Active, not recruiting
      • Florida cancer specialist/Sarah Cannon Research Institute
  • Ohio
    • Cleveland, Ohio, United States, 44195-0001
      • Recruiting
      • The Cleveland Clinic
      • Contact: Smitha Krishnamurthi, MD
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • MD Anderson Cancer Center
      • Contact: David Hong, MD
      • Contact: Mary Trahan
  • Washington
    • Seattle, Washington, United States, 98109
      • Recruiting
      • Fred Hutchinson Cancer Center
      • Contact: Rachael Safyan, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ADG126 in combination with Pembrolizumab (Trade name KEYTRUDA®); An 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.	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).; Other Names: KEYTRUDA®
Experimental: ADG126 and pembrolizumab (KEYTRUDA®) in combination with Trifluridine/Tipiracil-Bevacizumab; To 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.	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).; Other Names: KEYTRUDA®; 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.; Other Names: Lonsurf and Avastin
Experimental: ADG126 and pembrolizumab (KEYTRUDA®) in combination with fruquintinib; To 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.	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).; Other Names: KEYTRUDA®; Drug: Standard of care (Fruquintinib); The standard of care therapy, Fruquintinib, is approved for treating metastatic colorectal cancer (CRC) and various solid tumors.; Other Names: Fruzaqla
Experimental: Dose Optimization; The 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.	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).; Other Names: KEYTRUDA®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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 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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetic (PK) profile/parameters	Area under the time concentration curve (AUC) from time zero to infinity (AUC0-inf)	From first dose (Cycle 1 Day 1,) until the last dose (up to 2 years)
Maximum (peak) plasma concentration (Cmax)	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)	Time to maximum (peak) concentration (Tmax)	From first dose (Cycle 1 Day 1,) until the last dose (up to 2 years)
Trough concentration (Ctrough)	Trough concentration (Ctrough)	From first dose (Cycle 1 Day 1,) until the last dose (up to 2 years)
Incidence of ADAs	this will be summarized for all patients who received at least 1 administration of ADG126. efficacy and safety will be evaluated.	From first dose (Cycle 1 Day 1,) until the last dose (up to 2 years)
To assess the disease control rate (DCR)	this will be calculated as the proportion/percentage of patients with best overall response of CR,PR,SD or progressive disease will be calculated.	From first dose (Cycle 1 Day 1,) until the last dose (up to 2 years)
To assess the progression free survival (PFS)	PFS will be censored at the time of the last evaluable tumor assessment (RECISTv1.1 and iRECIST)	From first dose (Cycle 1 Day 1,) until the last dose (up to 2 years)
To assess the overall survival (OS)	This will be used to estimate median survival times where applicable.	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	The dose optimization arm will be used to access the efficacy outcome derived in the defined patient population	From first dose (Cycle 1 Day 1,) until the last dose (up to 2 years)

Collaborators and Investigators

• Sponsor: Adagene Inc
• Collaborators: Merck Sharp & Dohme LLC
• Investigators: Study Director: Jiping Zha, MD, PhD, Adagene Inc

Study record dates

Study Major Dates

• Study Start (Actual): June 15, 2022
• Primary Completion (Estimated): October 31, 2026
• Study Completion (Estimated): April 30, 2027

Study Registration Dates

• First Submitted: May 16, 2022
• First Submitted That Met QC Criteria: June 2, 2022
• First Posted (Actual): June 6, 2022

Study Record Updates

• Last Update Posted (Estimated): January 7, 2026
• Last Update Submitted That Met QC Criteria: January 6, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: ADG126-P001
• Additional Relevant MeSH Terms: Neoplasms; Health Services Administration; Health Care Quality, Access, and Evaluation; Amino Acids, Peptides, and Proteins; Proteins; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleic Acids, Nucleotides, and Nucleosides; Quality of Health Care; Quality Indicators, Health Care; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Pyrimidine Nucleosides; Pyrimidines; Nucleosides; Deoxyribonucleosides; Thymidine; Bevacizumab; Trifluridine; trifluridine tipiracil drug combination; Standard of Care; pembrolizumab; HMPL-013
• Other Study ID Numbers: ADG126-P001; KEYNOTE-C98, MK-3475-C98 (Other Identifier: Merck Sharp & Dohme LLC)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No