This is a multicenter, open-label, prospective, phase 2 study of trastuzumab, bevacizumab, and paclitaxel as second-line treatment for patients with HER2-positive advanced gastric cancer who had progressed on first-line chemotherapy including trastuzumab or anti-HER2 agents.

Trastuzumab has been administered at 6 mg/kg every 3 weeks after initial loading of 8 mg/kg during the first anticancer treatment, so in the second anticancer treatment, 4 mg/kg is administered every 2 weeks to maintain the same concentration. Bevacizumab is administered at 5 mg/kg at 2-weekly intervals used in metastatic colorectal cancer. Paclitaxel is administered on a standard schedule of 80 mg/m2 for 3 consecutive weeks followed by a 1-week break as an existing weekly regimen, and when side effects occur, the weekly dose is reduced by 25% to 60 mg/m2 for 3 weeks or administered every 2 weeks. Administer 80 mg/m2. Administration of this drug is set as one cycle of 4 weeks.

Inclusion Criteria:

1. HER2-positive advanced gastric cancer

   • Defined as IHC 2+, which is IHC 3+ or SISH + (or FISH) evaluated by laboratory tests. (SISH positivity is defined as the ratio of the HER2 gene copy number to the CEP17 signal ≥ 2.0)
   • or significant overexpression of HER2 protein on target proteomic analysis (multiple reaction monitoring)

2. Patients who have progressed in response to one systemic anticancer therapy for advanced gastric cancer

3. Patients who are willing and able to write a written consent form for this trial.

4. Patients aged 19 years or older at the time of signing the subject consent form.

5. Patients with measurable or evaluable lesions according to RECIST 1.1.

6. ECOG activity status 0, 1 or 2

7. as patients with adequate organ function

   • Absolute neutrophil (ANC) ≥1.0 x 109/L, platelet ≥100 x 109/L, hemoglobin ≥9 g/dL, serum creatinine ≤1.5 x ULN, total bilirubin ≤3.0 mg on laboratory tests within 2 weeks before starting treatment /dL, AST/ALT ≤5 x ULN
   • Echocardiogram EF ≥55% or MUGA scan ≥50%

Exclusion Criteria:

1. Patients who have received chemotherapy, radiation therapy, immunotherapy or targeted therapy for gastric cancer within the past 2 weeks.

2. Patients who have experienced Grade 3-4 gastrointestinal bleeding within 3 months

3. Patients who have experienced an arteriovascular embolism event, including but not limited to myocardial infarction, transient ischemic attack, cerebrovascular disorder, or unstable angina within 6 months

4. Ongoing or active infection, symptomatic congestive heart failure, unstable angina, symptomatic or poorly controlled cardiac arrhythmias, uncontrolled thrombotic or hemorrhagic disorders, or any other serious medical disorder not controlled in the investigator's judgment patient with

5. Patients with a history of gastrointestinal perforation or fistula within 6 months.

6. Concomitant diagnosis of cancer in another site or history of active malignant tumor within the past 3 years

   • Excluding fully cured basal cell carcinoma and thyroid cancer, in situ cervical cancer