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

Advanced/Metastatic Solid Tumors Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05405595
• Other study ID #: ADG126-P001
• Secondary ID: KEYNOTE-C98, MK-
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: June 15, 2022
• Est. completion date: September 30, 2025

Study information

• Verified date: February 2024
• Source: Adagene Inc
• Contact: Xiaohong She, MS
• Phone: 408-838-9296
• Email: kristine_she[@]adagene.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 combination regimens in patients with advanced/metastatic solid tumors. 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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 131
• Est. completion date: September 30, 2025
• Est. primary completion date: March 30, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 advanced or metastatic solid tumors, histologically or pathologically confirmed, who have progressed after all standard therapies, or for whom no further standard therapy exists. Dose Expansion Phase Only: Tumor tissues (archived or fresh biopsy) before treatment are required for all patients. Biopsies and tumor tissues after treatment are optional but preferred for patients with MSS-CRC and 2L anti-PD-1/anti-PD-L1 experienced NSCLC.

8. No prior immunotherapy

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 immune-mediated AE.

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.

Related Conditions & MeSH terms

• Advanced/Metastatic Solid Tumors
• Neoplasms

Intervention

Drug:
• ADG126
ADG126 and Pembrolizumab (KEYTRUDA®) combination treatment both will be dosed until progressive disease (PD), intolerable toxicities, withdrawals of consent, or up to 35 cycles.

Locations

Country	Name	City	State
Korea, Republic of	Chungbuk National University Hospital	Cheongju-si	Chungcheongbugdo
Korea, Republic of	Keimyung University Dongsan Hospital	Daegu
Korea, Republic of	Dong -A University Hospital	Seogu	Busan Gwangyeogsi
Korea, Republic of	CHA Bundang Medical Center, CHA university	Seongnam	Gyeonggido
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	KangBuk Samsung Hospital	Seoul
Korea, Republic of	Samsung Medical Center	Seoul	Seoul Teugbyeolsi
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	Severance Hospital Yonsei University Health System	Seoul
Korea, Republic of	The Catholic University of Korea Street. Vincent Hospital	Suwon	Gyeonggido
United States	City of Hope National Medical Center	Duarte	California
United States	Florida cancer specialist	Sarasota	Florida
United States	HonorHealth Research Institute	Scottsdale	Arizona

Sponsors (2)

Lead Sponsor	Collaborator
Adagene Inc	Merck Sharp & Dohme LLC

Countries where clinical trial is conducted

United States,  Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum tolerated dose (MTD) and RP2D for ADG126 in combination with pembrolizumab.	Number of participants experiencing maximum tolerated dose (MTD) in dose escalation levels	9 months
Primary	the safety and tolerability of ADG126 at escalating dose level in combination with pembrolizumab in adults with advanced metastatic solid tumors	Number of participants with adverse events as assessed by CTCAE v5.0	9 months
Primary	Access the preliminary antitumor activity of ADG126-pembrolizumab combination regimens	Number of Participants with preliminary antitumor activity	9 months
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	Trough concentration (Ctrough)	Trough concentration (Ctrough)	From first dose (Cycle 1 Day 1,) until the last dose (up to 2 years)
Secondary	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)
Secondary	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)
Secondary	To assess the progression free survival (PFS)	PFS will be censored at the time of the last evaluable tumor assessment (RECISTv1.1 and /or iRECIST)	From first dose (Cycle 1 Day 1,) until the last dose (up to 2 years)
Secondary	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)