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

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.

Inclusion criteria

• ≥18 years of age at the time of informed consent.
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
• Wash out period from previous antitumor therapies
• At least 1 measurable lesion at baseline according to the definition of RECIST v1.1.
• Adequate organ function.
• An archival tumor biopsy is required and should be taken within 2 years of enrollment. If not available, a fresh tumor biopsy is acceptable.
• 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.
• Dose Expansion Phase Only: Tumor tissues (archived tissue) before treatment are required for all patients.

Exclusion criteria

• Pregnant or breastfeeding females.
• Childbearing potential who does not agree to the use of contraception during the treatment period.
• Treatment with any investigational drug within washout period.
• Prior treatment with a PD-1, PD-L1 targeting agent or a next-generation anti-CTLA-4 therapy with enhanced ADCC function.
• History of significant irAEs or irAE.
• Central nervous system (CNS) disease involvement.
• History or risk of autoimmune disease.
• Patients requiring systemic treatment with corticosteroids or other immunosuppressive medications (>10 mg/day prednisone or equivalent).
• Any uncontrolled active infections requiring systemic antimicrobial treatment (viral, bacterial, or other), or uncontrolled or poorly controlled, asthma, chronic obstructive pulmonary disease (COPD).
• Major surgery within 4 weeks prior to the first dose of the study drug.
• Has had an allogeneic tissue/solid organ transplant.
• 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.
• A positive COVID-19 test within 14 days of Cycle 1 Day 1.
• History of Hypersensitivity or known to be allergic to protein drugs or recombinant protein.
• Active hemoptysis or central airway invasion by metastatic tumor.