This is a multicentre, Phase Ib/II Clinical Study of AK109 and AK104 With or Without Chemotherapy in Second-line Treatment of Advanced Gastric Adenocarcinoma or Gastroesophageal Junction Adenocarcinoma .

Inclusion Criteria:

1. Written and signed informed consent
2. Age ≥ 18 years but ≤ 75 years
3. ECOG of 0 or 1.
4. Estimated life expectancy of ≥3 months.
5. Histologically or cytologically documented advanced unresectable or metastatic gastric adenocarcinoma or gastroesophageal Junction (GEJ) adenocarcinoma.
6. At least one measurable lesion per RECIST v1.1.
7. Gastric adenocarcinoma or gastroesophageal junction (GEJ) adenocarcinoma with failure of first-line treatment with anti-PD-1/L1 and chemotherapy
8. Adequate organ function.
9. Have agreed to take effective contraception from the date of signing the informed consent form until 120 days after the last administration.

Exclusion Criteria:

1. Other invasive malignancies within 3 years, except for locally treatable (manifested as cured) malignancies, such as basal or skin squamous cell carcinoma, superficial bladder cancer, cervical or breast carcinoma in situ.
2. Any previous systemic therapy targeting VEGF or anti-VEGFR signaling pathways.
3. In addition to PD1 or PD-L1,Prior exposure to anti-CTLA-4 antibody, or any other antibody or drug therapy for T cell co-stimulatory or checkpoint pathways, such as ICOS or agonists (e.g. CD40, CD137, GITR and OX40 etc).
4. Known history of primary immunodeficiency virus infection.
5. Known history of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation.
6. Known history of interstitial lung disease.
7. Known history of active tuberculosis (TB).
8. Central nervous system (CNS) metastasis, meningeal metastasis, spinal cord compression, or leptomeningeal disease.
9. Patients with untreated chronic hepatitis B or HBV DNA exceeding 500IU/mL or active hepatitis C should be excluded. Patients with HCV antibody positive are eligible to participate in the study if the results of HCV RNA test show negative.
10. Known history of testing positive for human immunodeficiency virus (HIV).
11. Uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated drainage.
12. Subjects with active, known or suspected autoimmune disease, or a medical history of autoimmune disease, with the exceptions of the following: vitiligo, alopecia, Grave disease, psoriasis or eczema not requiring systemic treatment within the last 2 years, hypothyroidism (caused by autoimmune thyroiditis) only requiring steady doses of hormone replacement therapy and type I diabetes only requiring steady doses of insulin replacement therapy, or completely relieved childhood asthma that requires no intervention in adulthood, or primary diseases that will not relapse unless triggered by external factors.
13. Pregnant or lactating women.