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

Phase 1

Recruiting

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

• Registration Number: NCT05405595
• Lead Sponsor: Adagene Inc

Brief Summary

This is a Phase 1b/2, open-label, dose escalation study to evaluate the safety, tolerability, PK, and immunogenicity of ADG126-pembrolizumab combination regimens in patients with advanced/metastatic solid tumors.

Detailed Description

This is a Phase 1b/2, open-label, multicenter, dose escalation and dose expansion study to evaluate the safety, tolerability, PK, and preliminary efficacy of ADG126-Pembrolizumab alone or ADG126-Pembrolizumab in combination with trifluridine/tipiracil-bevacizumab or fruquintinib in patients with advanced/metastatic solid tumors, with a focus on MSS CRC.

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 Timeline

• Study First Submitted: 2022-05-16
• Study First Submitted QC: 2022-06-02
• Study First Posted: 2022-06-06
• Study Start: 2022-06-15
• Status Verified: 2025-05
• Last Update Submitted: 2025-05-30
• Last Update Posted: 2025-06-04
• Primary Completion: 2026-10-31
• Study Completion: 2027-04-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 152

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 or fresh biopsy) 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 an anti-CTLA-4 therapy.
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 severe Hypersensitivity (Grade ≥3)or known to be allergic to protein drugs or recombinant protein.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
ADG126 in combination with Pembrolizumab (Trade name KEYTRUDA®)	ADG126	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.
ADG126 in combination with Pembrolizumab (Trade name KEYTRUDA®)	Pembrolizumab (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.
ADG126 and pembrolizumab (KEYTRUDA®) in combination with Trifluridine/Tipiracil-Bevacizumab	ADG126	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.
ADG126 and pembrolizumab (KEYTRUDA®) in combination with Trifluridine/Tipiracil-Bevacizumab	Pembrolizumab (KEYTRUDA®)	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.
ADG126 and pembrolizumab (KEYTRUDA®) in combination with fruquintinib	Pembrolizumab (KEYTRUDA®)	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.
ADG126 and pembrolizumab (KEYTRUDA®) in combination with Trifluridine/Tipiracil-Bevacizumab	Standard of Care (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.
ADG126 and pembrolizumab (KEYTRUDA®) in combination with fruquintinib	ADG126	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.
ADG126 and pembrolizumab (KEYTRUDA®) in combination with fruquintinib	Standard of care (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.

Primary Outcome Measures

Name	Time	Method
Access the preliminary antitumor activity of ADG126-pembrolizumab combination regimens	9 months	Number of Participants with preliminary antitumor activity
Maximum tolerated dose (MTD) and RP2D for ADG126 in combination with pembrolizumab.	9 months	Number of participants experiencing maximum tolerated dose (MTD) in dose escalation levels
the safety and tolerability of ADG126 at escalating dose level in combination with pembrolizumab in adults with advanced metastatic solid tumors	9 months	Number of participants with adverse events as assessed by CTCAE v5.0
Maximum tolerated dose (MTD) and/or RP2D for ADG126 with Trifluridine/Tipiracil-Bevacizumab	6 months	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:
Access the preliminary antitumor activity of ADG126 with Pembrolizumab in combination standard of care	6 months	To assess the preliminary antitumor activity of ADG126 + pembrolizumab in combination with the following SOC therapies in MSS CRC (Trifluridine/tipiracil-bevacizumab); SOC (Fruquintinib)

Secondary Outcome Measures

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

Trial Locations

Locations (17)

Honor Health Research Institute; 🇺🇸 Scottsdale, Arizona, United States

Florida cancer specialist/Sarah Cannon Research Institute; 🇺🇸 Sarasota, Florida, United States

Fujian Cancer Hospital; 🇨🇳 Fuzhou, Fujian, China

SunYat-Sen University Cancer Center; 🇨🇳 Guangzhou, Guang Dong, China

Hong Kong Humanity & Health Clinical Trial Center; 🇨🇳 Hong Kong, Hong Kong, China

Prince of Wales Hospital; 🇨🇳 Hong Kong, Hong Kong, China

City of Hope National Medical Center; 🇺🇸 Duarte, California, United States

Dong -A University Hospital; 🇰🇷 Seogu, Busan Gwangyeogsi, Korea, Republic of

Chungbuk National University Hospital; 🇰🇷 Cheongju-si, Chungcheongbugdo, Korea, Republic of

CHA Bundang Medical Center, CHA university; 🇰🇷 Seongnam, Gyeonggido, Korea, Republic of

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