This is a multi-center, open label, phase Ib/II clinical study of AK109 and AK104 to evaluate the safety, tolerability, effectiveness, pharmacokinetic characteristics in advanced solid tumors .

Inclusion Criteria:

1. Written and signed informed consent.
2. Age ≥ 18 years and ≤ 75 years.
3. ECOG Performance Status of 0 or 1.
4. Estimated life expectancy of ≥3 months.
5. Histologically or cytologically documented, locally advanced or metastatic solid tumours (NSCLC, mCRC, HCC, GEJ, etc. ), for which standard therapy does not exist or has proven ineffective or intolerable.
6. At least one radiographically measurable lesion per RECIST 1.1.
7. Tumor biopsy (during advanced stage) available.
8. Adequate organ function.
9. Female participants of childbearing potential and male partners with female partners of childbearing potential must agree to use effective barrier methods of contraception during the study and for 120 days after last dose of study drug.

Exclusion Criteria:

1. Other documented active malignancies other than for this trial within 3 years.
2. Participation in other clincial trials simultaneously.
3. Use of systemic anti-tumor treatments with 4 weeks, non-specific immunomodulating agents within 2 weeks.
4. Prior exposure to other T cell coregulatory proteins except for PD-1/PD-L1 inhibitors (apart from cohort B, i.e. treatment naive HCC patients).
5. Current use corticosteroids/immunosuppressive agents, permanently discontinuation of study drug, or having any unresolved irAEs (≥grade 2) from prior PD-1/PD-L1 inhibitors treatment.
6. Central nervous system (CNS) metastasis, meningeal metastasis, spinal cord compression, or leptomeningeal disease.
7. Uncontrolled pleural/pericardial or peritoneal effusion.
8. History of hemorrhagic event need blood transfusion, invasive approaches to intervene, or hospitalization within 3 months, or having high risks of bleeding.
9. Any thromboembolic event, non-gastrointestinal fistula or female genital tract fistula within 6 months.
10. Uncontrolled gastrointestinal diseases.
11. Use of NSAIDs and anticoagulant agents within 7 days.
12. Major surgical procedure, open biopsy, or significant traumatic injury within 4 weeks.
13. Severe or uncontrolled hypertension and cardiovascular/cerebrovascular diseases.
14. Uncontrolled comorbidities need corticosteroids using.
15. Active or prior autoimmune disease or history of immunodeficiency.
16. History of interstitial lung disease.
17. Known history of active tuberculosis (TB).
18. Evidence of active infections including hepatitis B and C.
19. Use of anti-infectious agents within 2 weeks.
20. History of human immunodeficiency virus (HIV) infections.
21. Active syphilis infections.
22. Any unresolved toxicities (≥grade 2) from previous anti-cancer therapies.
23. Mental illness, drug abuse, or alcohol dependence that may affect compliance with the test requirements.