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

Phase 1

Recruiting

• Conditions: Advanced/Metastatic Solid Tumors
• Interventions: Drug: ADG126

• 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 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).

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: 2024-02
• Last Update Submitted: 2024-02-23
• Last Update Posted: 2024-02-26
• Primary Completion: 2025-03-30
• Study Completion: 2025-09-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 131

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

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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.

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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.

Primary Outcome Measures

Name	Time	Method
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
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

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)
Trough concentration (Ctrough)	From first dose (Cycle 1 Day 1,) until the last dose (up to 2 years)	Trough concentration (Ctrough)
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.
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)
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.
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)
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 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 /or iRECIST)

Trial Locations

Locations (13)

Florida cancer specialist; 🇺🇸 Sarasota, Florida, United States

Asan Medical Center; 🇰🇷 Seoul, Korea, Republic of

Keimyung University Dongsan Hospital; 🇰🇷 Daegu, Korea, Republic of

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

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

Samsung Medical Center; 🇰🇷 Seoul, Seoul Teugbyeolsi, Korea, Republic of

Seoul National University Hospital; 🇰🇷 Seoul, Korea, Republic of

KangBuk Samsung Hospital; 🇰🇷 Seoul, Korea, Republic of

Severance Hospital Yonsei University Health System; 🇰🇷 Seoul, Korea, Republic of

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

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

The Catholic University of Korea Street. Vincent Hospital; 🇰🇷 Suwon, Gyeonggido, Korea, Republic of

HonorHealth Research Institute; 🇺🇸 Scottsdale, Arizona, United States