A Study to Evaluate the Safety, Pharmacokinetics, and Antitumor Activity of AK114

A Phase 1a, Multicenter, Open-label, Dose-escalation Study to Evaluate the Safety, Pharmacokinetics, and Antitumor Activity of AK114 in Subjects With Advanced or Metastatic Solid Tumors

A Phase 1 study to evaluate the safety, tolerability, PK, immunogenicity, pharmacodynamics, and preliminary antitumor activity of AK114.

This is a first-in-human (FIH), Phase 1a, multicenter, open-label, single-arm dose-escalation study of AK114 to evaluate the safety, tolerability, PK, pharmacodynamics, antitumor activity and immunogenicity in adult subjects with advanced or metastatic solid tumors. The study is comprised of dose escalation phase. Approximately 30 subjects will be treated in this study.

Inclusion Criteria:

1. Written and signed informed consent
2. Age ≥ 18
3. Subjects must have histologically or cytologically confirmed advanced or metastatic solid tumor
4. Subject must have at least one measurable lesion according to RECIST v1.1
5. Eastern Cooperative Oncology Group (ECOG) performance status score ≤ 1
6. At the time of Day 1 of the study, subjects with central nervous system (CNS) metastases must have been treated
7. Available archived tumor tissue sample (block or a minimum of 10 unstained slides of formalin-fixed paraffin-embedded tissues) to allow for correlative biomarker studies
8. Subjects may opt to provide two fresh biopsy samples (pretreatment and on treatment), where clinically appropriate
9. Adequate organ function
10. Use acceptable method of contraception from screening, and must agree to continue for 120 days after the final dose of investigational product

Exclusion Criteria:

1. History of severe hypersensitivity reactions to other monoclonal antibodies
2. History or concurrent gastrointestinal perforation, surgery and wound healing complications, hemorrhage events
3. Patients with clinically significant cardiovascular disease
4. Subjects with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of investigational product administration
5. Active or prior documented autoimmune disease within the past 2 years
6. History of primary immunodeficiency
7. History of organ transplant or hematopoietic stem cell that requires use of immunosuppressive medications
8. Known allergy or reaction to any component of the investigational product formulation.
9. History of interstitial lung disease or noninfectious pneumonitis except for those induced by radiation therapies.
10. Prior treatment with canakinumab.