Study of Camrelizumab (SHR-1210) and Apatinb Based Therapies for Alpha-fetoprotein (AFP)-Producing Gastric Cancer or Gastroesophageal Junction Adenocarcinoma

Eligibility

Criteria

Inclusion Criteria:

          1. Patients who provided written informed consent to be subjects in this trial

          2. Aged ≥18 years

          3. Performance status of 0 to 2 on the Eastern Cooperative Oncology Group (ECOG)
             Performance Scale

          4. Has histologically-confirmed diagnosis of locally advanced unresectable or metastatic
             gastric or GEJ adenocarcinoma

          5. Clinical staging was performed according to enhanced CT/MRI examination (combined with
             endoscopic ultrasonography and diagnostic laparoscopic exploration if necessary). For
             patients with locally advanced or metastatic gastric/GEJ cancer in stage III-IV (AJCC
             8 edition TNM stage) that could not be resected, the possibility of resectable was
             determined by MDT

          6. For cohort 1, no prior systemic chemotherapy for the treatment of the participant's
             advanced or metastatic disease (treatment with chemotherapy and/or radiation as part
             of neoadjuvant/adjuvant therapy is allowed as long as completed at least 6 months
             prior to the diagnosis of advanced or metastatic disease); for cohort 2, received and
             progressed on ≥1 prior systemic therapy for their advanced disease.

          7. Have measurable disease as defined by RECIST 1.1 as determined by investigator
             assessment

          8. Serum AFP > 2 upper limit of normal (ULN) or AFP positive by immunohistochemical
             staining methods

          9. Adequate Organ Function Laboratory Values:

             Hemoglobin ≥90g/L; Absolute neutrophil count (ANC) ≥1.5×109/L; Platelets ≥80×109/L;
             AST and ALT ≤ 2.5 ULN or ≤ 5 ULN for subjects with liver metastases; Total bilirubin
             ≤1.5 ULN; Serum creatinine ≤1.5 ULN or measured or calculated creatinine clearance >
             50ml/min; Albumin ≥ 30g/L;

         10. No serious concomitant disease result in survival of less than 5 years

         11. Patients capable of taking oral medication

         12. Have good compliance and be able to follow the study protocol

         13. Female subjects of childbearing potential must have a negative urine or serum
             pregnancy test within 72 hours prior to receiving the first dose of study medication
             and must be willing to use an adequate method of contraception for the course of the
             study through 90 days after the last dose of study medication. Male subjects of
             childbearing potential must agree to use an adequate method of contraception starting
             with the first dose of study therapy through 90 days after the last dose of study
             therapy

         14. Agree to provide blood and/or tumor tissue sample deemed adequate for PD-L1 and other
             biomarker analysis.

        Exclusion Criteria:

          1. Is pregnant or breastfeeding

          2. HER2 positive subjects will be excluded from cohort 1

          3. Patients have recovered adverse events associated with pretreatment to Grade 1 or
             lower with CTCAE v5.0 excluding alopecia

          4. Patients have an active malignancy (except for definitively treated basal cell
             carcinoma of the skin, or carcinoma-in-situ of the cervix) within the past 5 years

          5. Active heart disease that is not well controlled, e.g. symptomatic coronary heart
             disease, New York Heart Association (NYHA) congestive heart failure of grade II or
             above, severe arrhythmias requiring drug intervention, myocardial infarction within
             the past 12 months, QTc ≥ 450ms for male, QTc ≥ 450ms for female, LVEF<50%

          6. Genetic or acquired bleeding and thrombotic tendencies (e.g., hemophilia, coagulation
             disorders, thrombocytopenia, etc.)

          7. Patients with a history of gastrointestinal perforation, intra-abdominal abscess, or
             in-three-months ileus

          8. Coagulation disorders (International normalized ratio, INR > 2.0 or Prothrombin time,
             PT > 16s)

          9. Organ transplantation requires immunosuppressants, or who have received
             immunosuppressants/systemic corticosteroids therapy <14 days before first dose for an
             immunosuppression purpose (> 10mg/day prednisone or other equivalency drugs)

         10. Patients have an active ulcer, serious non-healing wound, or bone fracture

         11. Patients with hypertension that is difficult to control (systolic blood pressure ≥140
             mmHg and diastolic blood pressure ≥90 mmHg) despite treatment with several hypotensive
             agents

         12. Patients have a deficiency of dihydropyrimidine dehydrogenase (DPD) will be excluded
             from cohort 1

         13. Have any contraindications for study treatment

         14. Patients with a history of prior treatment with Apatinib or any anti-PD-1, anti-PD-L1
             agent

         15. Urinary protein is more than 2+ and 24-hour urine protein > 1.0g

         16. Patients with active hepatitis B (HBsAg positive and HBV DNA≥500 IU/ml), hepatitis C
             (HCV antibodies positive and HCV RNA copies > ULN); with active infection requiring
             drug intervention

         17. Patients with active symptoms or signs of interstitial lung disease

         18. Patients with concurrent autoimmune disease, or a history of chronic or recurrent
             autoimmune disease

         19. Patients were judged unsuitable as subjects of this trial by investigators.

• Gender: all
• Age: 18
• Healthy volunteers: no
• Therapy type: -
• Therapy Specification: -