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

Adagene

Status and phase: Enrolling; Phase 2; Phase 1

Conditions: Advanced/Metastatic Solid Tumors

Treatments: Drug: Standard of Care (Trifluridine/Tipiracil-Bevacizumab); Drug: Standard of care (Fruquintinib); Drug: ADG126; Drug: Pembrolizumab (KEYTRUDA®)

Study type: Interventional

Funder types: Industry

Identifiers

NCT05405595

ADG126-P001

KEYNOTE-C98, MK-3475-C98 (Other Identifier)

Details and patient eligibility

About

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).

Full 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.

Enrollment: 186 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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186 participants in 4 patient groups

ADG126 in combination with Pembrolizumab (Trade name KEYTRUDA®)

Experimental group

Description:

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.

Treatment:

Drug: Pembrolizumab (KEYTRUDA®)

Drug: ADG126

ADG126 and pembrolizumab (KEYTRUDA®) in combination with Trifluridine/Tipiracil-Bevacizumab

Experimental group

Description:

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.

Treatment:

Drug: Pembrolizumab (KEYTRUDA®)

Drug: ADG126

Drug: Standard of Care (Trifluridine/Tipiracil-Bevacizumab)

ADG126 and pembrolizumab (KEYTRUDA®) in combination with fruquintinib

Experimental group

Description:

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.

Treatment:

Drug: Pembrolizumab (KEYTRUDA®)

Drug: ADG126

Drug: Standard of care (Fruquintinib)

Dose Optimization

Experimental group

Description:

The randomized phase 2 Dose Optimization arm is intended to test two dosing regimens of ADG126 in combination with pembrolizumab (KEYTRUDA®), which allows the selection of an optimal regimen. The study treatments may continue for up to 35 treatments for pembrolizumab (KEYTRUDA®) if given every 21 days and 18 treatments for pembrolizumab (KEYTRUDA®) if given every 42 days until PD, intolerable toxicities or withdrawal of consent.

Treatment:

Drug: Pembrolizumab (KEYTRUDA®)

Drug: ADG126