A Study of AK104 in the First-line Treatment of Locally Advanced Unresectable or Metastatic G/GEJ Adenocarcinoma

Inclusion Criteria:

• Subjects must meet all of the following inclusion criteria to be enrolled in thestudy:

1. Ability to understand and voluntarily sign a written informed consent form (ICF), which must be signed before the specified study procedures required forthe study are performed.

2. Males or females aged ≥ 18 to ≤ 75 years at the time of signing informedconsent.

3. Histopathologically confirmed gastric adenocarcinoma or gastroesophagealjunction (GEJ) adenocarcinoma.

4. Unresectable locally advanced or metastatic gastric adenocarcinoma or GEJadenocarcinoma.

5. Subjects have not received prior systemic therapy for locally advanced ormetastatic gastric adenocarcinoma or adenocarcinoma of the gastroesophagealjunction. For subjects who have received prior neoadjuvant/adjuvantchemotherapy or chemoradiotherapy for curative intent, the time between diseaseprogression and last treatment should be at least 6 months.

6. Subjects have at least one measurable tumor lesion per RECIST v1.1; lesionsthat received radiotherapy are not selected as target lesions, unless thelesion is the only measurable lesion and has unequivocal progression as judgedby imaging, it can be considered as a target lesion.

Exclusion Criteria:

• Subjects who meet any of the following criteria are not eligible to participate inthis study:

1. Subjects with known HER2-positive gastric or GEJ adenocarcinoma.

2. Histopathology or cytology confirmed other pathological types, such as squamouscell carcinoma, sarcoma, or undifferentiated carcinoma.

3. Subjects who received palliative local therapy for non-target lesions within 2weeks prior to the first dose; systemic nonspecific immunomodulatory therapy (e.g., interleukin, interferon, thymosin, etc.) within 2 weeks prior to thefirst dose; and Chinese herbal medicine or traditional Chinese medicinalproducts with anti-tumor indications within 2 weeks prior to the first dose.

4. Subjects who received any prior treatments targeting the mechanism of tumorimmunity.

5. Medical history of gastrointestinal perforation or gastrointestinal fistulawithin 6 months prior to the first dose. If the perforation or fistula has beentreated with resection or repair and the disease has recovered or resolved asjudged by the Investigator, enrollment may be allowed.

6. Active or previously documented inflammatory bowel disease (e.g., Crohn'sdisease or ulcerative colitis).

7. Active malignancies within the past 3 years, with the exception of tumors inthis study and cured local tumors, such as basal cell carcinoma of skin,squamous cell carcinoma of skin, superficial bladder cancer, carcinoma in situof cervix, carcinoma in situ of breast, localized prostate cancer, etc.

8. Known active or untreated brain metastases, meningeal metastases, spinal cordcompression, or leptomeningeal disease.

9. Presence of clinically symptomatic pleural effusion, pericardial effusion, orascites requiring frequent drainage (≥ 1/month).

10. Active autoimmune disease requiring systemic treatment within 2 years prior tothe start of study treatment, or autoimmune diseases that may relapse orrequire scheduled treatment as judged by the Investigator.