A Study of AK109 and AK104 in 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 metastaticgastric adenocarcinoma or gastroesophageal Junction (GEJ) adenocarcinoma.

6. At least one measurable lesion per RECIST v1.1.

7. Gastric adenocarcinoma or gastroesophageal junction (GEJ) adenocarcinoma withfailure 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 informedconsent form until 120 days after the last administration.

Exclusion Criteria:

1. Other invasive malignancies within 3 years, except for locally treatable (manifestedas cured) malignancies, such as basal or skin squamous cell carcinoma, superficialbladder 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 otherantibody or drug therapy for T cell co-stimulatory or checkpoint pathways, such asICOS 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 stemcell transplantation.

6. Known history of interstitial lung disease.

7. Known history of active tuberculosis (TB).

8. Central nervous system (CNS) metastasis, meningeal metastasis, spinal cordcompression, or leptomeningeal disease.

9. Patients with untreated chronic hepatitis B or HBV DNA exceeding 500IU/mL or activehepatitis C should be excluded. Patients with HCV antibody positive are eligible toparticipate 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 repeateddrainage.

12. Subjects with active, known or suspected autoimmune disease, or a medical history ofautoimmune disease, with the exceptions of the following: vitiligo, alopecia, Gravedisease, psoriasis or eczema not requiring systemic treatment within the last 2years, hypothyroidism (caused by autoimmune thyroiditis) only requiring steady dosesof hormone replacement therapy and type I diabetes only requiring steady doses ofinsulin replacement therapy, or completely relieved childhood asthma that requiresno intervention in adulthood, or primary diseases that will not relapse unlesstriggered by external factors.

13. Pregnant or lactating women.