This phase I trial is trying to understand how safe a new targeted cancer therapy is, and how much of it to use, as a combination treatment for patients with advanced solid cancers that have spread to other parts of the bodyA Phase 1a/1b, Multicenter, Open-Label, Dose-Escalation and Dose-Expansion Study to Evaluate the Safety, Pharmacokinetics, and Anti-tumor Activity of AK119 in Combination With AK104 in Subjects With Advanced or Metastatic Solid Tumors.

Exclusion

1. Receipt of the following treatments or procedures:

   1. Anticancer small-molecule targeted agent (e.g., tyrosine kinase inhibitor) within 2 weeks prior to the first dose of investigational product;
   2. Anti-PD-1/PD-L1 mAb within 4 weeks prior to the first dose of investigational product;
   3. Prior use of approved or investigational anti-CTLA-4 therapy, anti-CD73 therapy or adenosine 2A receptor inhibitors, or any other antibody or drug targeting T cell costimulation or immune checkpoint pathways such as ICOS, or agonists such as CD40, CD137, GITR, OX40 etc.
   4. Other anticancer mAb within 4 weeks or 5 half-lives (whichever is less) prior to the first dose of investigational product;
   5. Other anticancer therapy (e.g., chemotherapy, radiotherapy, etc.) within 4 weeks prior to the first dose of investigational product; [Note: Palliative radiotherapy > 1 week prior to first dose is allowed]
   6. Any major surgery (e.g., laparotomy, thoracotomy, removal of organ[s]) within 4 weeks prior to the first dose of investigational product;
   7. Any other non-approved investigational product or procedure within 4 weeks prior to the first dose of investigational product, or concurrent participation in another therapeutic clinical study;
2. Any condition that required systemic treatment with corticosteroids (> 10 mg daily prednisone or equivalent) or other immunosuppressive agents within 14 days prior to the first dose of investigational product.
3. Receipt of live attenuated vaccines within 4 weeks prior to the first dose of investigational product; Note: seasonal vaccine for influenza which is generally inactivated is allowed.
4. Prior organ transplantation;
5. Prior malignancy active within the previous 3 years except for the tumor for which a subject is enrolled in the study, and locally curable cancers that have been apparently cured, such as basal cell cancer or carcinoma in situ of the cervix or breast;
6. Subjects with history of brain metastases that have been treated may participate provided they show evidence of stable supra-tentorial lesions at Screening (based on 2 sets of brain images, performed ≥ 4 weeks apart, and obtained after the brain metastases treatment).
7. Active infections (including tuberculosis) requiring systemic antibacterial, antifungal, or antiviral therapy within 14 days prior to the first dose of investigational products. Note: antiviral therapy is permitted for patients with viral hepatitis;
8. Known history of human immunodeficiency virus (HIV) infection;
9. Known active hepatitis B or C infections (Active hepatitis B is defined as a known positive Hepatitis B surface antigen [HBsAg] result. Active hepatitis C is defined by a known positive Hepatitis C virus [HCV] antibody with detectable HCV ribonucleic acid [RNA] results);
10. Active autoimmune diseases or history of autoimmune diseases that may relapse. Note: Subjects with controlled type 1 diabetes mellitus, thyroiditis in euthyroid state or hypothyroidism well managed by hormone replacement therapy (HRT), or skin diseases not requiring systemic treatment (e.g., vitiligo, psoriasis) are eligible;
11. History of interstitial lung disease, noninfectious pneumonitis except for those induced by radiation therapies;
12. Uncontrolled massive ascites or pleural effusion, as determined by the Investigator;
13. Patients with clinically significant cardio-cerebrovascular or venous thromboembolic disease.
14. Mean QT interval corrected for heart rate using Fridericia's formula (QTcF) ≥ 470 msec calculated from 3 ECGs (within 5 minutes at least 1 minute apart);
15. Uncontrolled intercurrent illness including, but not limited to, uncontrolled hypertension, uncontrolled diabetes, uncontrolled endocrinopathy, severe active peptic ulcer disease or gastritis, or psychiatric illness/social situations that would limit compliance with study requirement or compromise the ability of the subject to give written informed consent;
16. History of severe hypersensitivity reactions to other mAbs;
17. Toxicities of prior anticancer therapy have not resolved to NCI-CTCAE version 5.0 Grade ≤1, or to levels dictated in the inclusion/exclusion criteria, except toxicities not considered a safety risk (e.g., alopecia, neuropathy, or asymptomatic laboratory abnormalities);
18. Pregnant or breastfeeding women;
19. Any other conditions that, in the opinion of the Investigator, would interfere with evaluation of the investigational product or interpretation of subject safety or study results.