Clinical trial NCT05405595: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Advanced/Metastatic Solid Tumors
Keywords: ADG126-P001
Lead sponsor: Adagene Inc
Sponsor class: INDUSTRY
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2022-06-06
Enrollment: 152
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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).

Eligibility criteria: 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.

Primary outcomes:
measure: Maximum tolerated dose (MTD) and RP2D for ADG126 in combination with pembrolizumab.
timeFrame: 9 months
measure: the safety and tolerability of ADG126 at escalating dose level in combination with pembrolizumab in adults with advanced metastatic solid tumors
timeFrame: 9 months
measure: Access the preliminary antitumor activity of ADG126-pembrolizumab combination regimens
timeFrame: 9 months
measure: Maximum tolerated dose (MTD) and/or RP2D for ADG126 with Trifluridine/Tipiracil-Bevacizumab
timeFrame: 6 months
measure: Access the preliminary antitumor activity of ADG126 with Pembrolizumab in combination standard of care
timeFrame: 6 months
Secondary outcomes:
measure: Pharmacokinetic (PK) profile/parameters
timeFrame: From first dose (Cycle 1 Day 1,) until the last dose (up to 2 years)
measure: Maximum (peak) plasma concentration (Cmax)
timeFrame: From first dose (Cycle 1 Day 1,) until the last dose (up to 2 years)
measure: Time to maximum (peak) concentration (Tmax)
timeFrame: From first dose (Cycle 1 Day 1,) until the last dose (up to 2 years)
measure: Trough concentration (Ctrough)
timeFrame: From first dose (Cycle 1 Day 1,) until the last dose (up to 2 years)
measure: Incidence of ADAs
timeFrame: From first dose (Cycle 1 Day 1,) until the last dose (up to 2 years)
measure: To assess the disease control rate (DCR)
timeFrame: From first dose (Cycle 1 Day 1,) until the last dose (up to 2 years)
measure: To assess the progression free survival (PFS)
timeFrame: From first dose (Cycle 1 Day 1,) until the last dose (up to 2 years)
measure: To assess the overall survival (OS)
timeFrame: From first dose (Cycle 1 Day 1,) until the last dose (up to 2 years)
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Honor Health Research Institute
state: Arizona
city: Duarte
country: United States
facility: City of Hope National Medical Center
state: California
city: Sarasota
country: United States
facility: Florida cancer specialist/Sarah Cannon Research Institute
state: Florida
city: Fuzhou
country: China
facility: Fujian Cancer Hospital
state: Fujian
city: Guangzhou
country: China
facility: SunYat-Sen University Cancer Center
state: Guang Dong
city: Hong Kong
country: China
facility: Hong Kong Humanity & Health Clinical Trial Center
state: Hong Kong
city: Hong Kong
country: China
facility: Prince of Wales Hospital
state: Hong Kong
city: Seogu
country: Korea, Republic of
facility: Dong -A University Hospital
state: Busan Gwangyeogsi
city: Cheongju-si
country: Korea, Republic of
facility: Chungbuk National University Hospital
state: Chungcheongbugdo
city: Seongnam
country: Korea, Republic of
facility: CHA Bundang Medical Center, CHA university
state: Gyeonggido
city: Suwon
country: Korea, Republic of
facility: The Catholic University of Korea Street. Vincent Hospital
state: Gyeonggido
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
state: Seoul Teugbyeolsi
city: Daegu
country: Korea, Republic of
facility: Keimyung University Dongsan Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: KangBuk Samsung Hospital
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Severance Hospital Yonsei University Health System
Study officials:
affiliation: Adagene Inc
name: Jiping Zha, MD, PhD
role: STUDY_DIRECTOR
References: