Advanced/Metastatic Solid Tumors
Conditions
Keywords
ADG126-P001
Brief summary
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).
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.
Interventions
DRUGADG126
ADG126 is an anti-CTLA-4 fully human monoclonal antibody that specifically binds to human CTLA-4.
DRUGPembrolizumab (KEYTRUDA®)
Pembrolizumab (KEYTRUDA®) is a PD-1 receptor-blocking antibody (a humanized IgG4 monoclonal antibody).
DRUGStandard 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.
DRUGStandard of care (Fruquintinib)
The standard of care therapy, Fruquintinib, is approved for treating metastatic colorectal cancer (CRC) and various solid tumors.
Sponsors
Merck Sharp & Dohme LLC
Adagene Inc
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum tolerated dose (MTD) and RP2D for ADG126 in combination with pembrolizumab. | 9 months | To determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) for ADG126+ pembrolizumab 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 | Incidence rate of AEs 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/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) |
| Access and characterize the optimal dose based on safety and efficacy parameters | 9 months | To characterize the optimal dose based on safety and efficacy parameters |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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) |
| 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) |
| To assess the efficacy outcomes in the defined patient population | From first dose (Cycle 1 Day 1,) until the last dose (up to 2 years) | The dose optimization arm will be used to access the efficacy outcome derived in the defined patient population |
| 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) |
| 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. |
Countries
China, South Korea, United States
Contacts
Primary ContactXiaohong She, MS
Backup ContactJiping Zha, MD, PhD
Outcome results
None listed