A Study of AK104/Placebo Plus AK109/Placebo And Paclitaxel in Gastric or Gastroesophageal Junction Adenocarcinoma

Prior treatment

• Received prior systemic anti-tumour therapy within 4 weeks before randomization
• Previous systemic treatment with taxane within 6 months before randomization
• Previous systemic treatment targeting VEGF or anti-VEGFR signaling pathways
• In addition to anti-PD-(L)1 monoclonal antibody, prior exposure to other immune checkpoint inhibitors, immune checkpoint agonists, immune cell therapy or other therapy that targets anti-tumor immune mechanisms
• History of immune-related adverse effects leading to recommendation against reintroduction of immunotherapy or any condition dependency on systemic therapy with glucocorticoids or immunosuppressive agents within 14 days prior to randomization
• History of severe infection within 4 weeks prior to randomization
• History or presence of a serious hemorrhage or known bleeding tendency within 2 months before randomization
• Major surgical procedure or serious trauma within 28 days prior to randomization
• Toxicities of prior anticancer therapy have not resolved to ≤ Grade 1 (NCI-CTCAE version 5.0)
• Use of live vaccines within 30 days prior to randomization

Other illness

• Mixed gastric or gastroesophageal Junction cancer containing other pathological components than adenocarcinoma
• Known other invasive malignancies within 3 years
• History of interstitial lung disease or noninfectious pneumonitis
• Active infectious diseases, including tuberculosis, HIV infection, syphilis infection，or hepatitis B/C
• Known allergy to the antibody or any component of the study drug; Or the constitution of being allergic to multiple substances
• History of allogeneic organ transplantation or allogeneic haematopoietic stem cell transplantation
• Any condition considered by the investigator to be inappropriate for enrollment

Other

• HER2-positive
• Subjects who are currently participating in other interventional study
• Presence of central nervous system metastases, leptomeningeal metastases, or spinal cord compression
• Uncontrolled pleural effusion, pericardial effusion or ascites requiring repeated drainage
• Pregnant or lactating women.

• Signed informed consent
• Age ≥ 18 years and ≤ 75 years
• Histologically or cytologically documented advanced unresectable or metastatic gastric adenocarcinoma or gastroesophageal Junction (GEJ) adenocarcinoma.
• Failed first-line treatment with PD-(L)1 monoclonal antibody and standard chemotherapy
• At least one measurable disease based on RECIST v1.1
• ECOG status of 0 or 1
• Estimated survival ≥ 3 months
• Adequate organ function per protocol-defined criteria
• Women of childbearing potential and men with female partners of childbearing potential must agree to use effective contraception during treatment and for at least 120 days following the last dose of study treatment