A Study of Trastuzumab in Combination With Capecitabine and Cisplatin in Patients With Tissue HER2- But Serum HER2+ AGC

Prior treatment

• Patients who previously received chemotherapy for advanced/metastatic diseases (adjuvant/neoadjuvant chemotherapy, completed at least 6 months prior to enrollment in this clinical study, is permitted, but platinum-based adjuvant/neoadjuvant chemotherapy is not permitted).
• Patients with relevant toxicities remaining following previous curative therapy (except for alopecia). For example, neurotoxicity ≥ grade 2 based on NCI-CTCAE version 5.0.
• Patients who are treated with long-term or high-dose corticosteroids (steroid inhalation or short-term use of oral steroids for vomiting inhibition and appetite stimulation is permitted).
• Patients who are treated with another investigational product within 4 weeks prior to the initiation of treatment in this clinical study.
• Patients receiving radiation therapy within 4 weeks prior to the initiation of treatment with the study drug (palliative radiation curative therapy that is partially carried out for bone metastasis. Washout period of 2 weeks is also permitted in patients recovered from all acute toxicities.).
• Patients who underwent major surgery within 4 weeks prior to the initiation of treatment with the study drug and have not yet been completely recovered.

Other illness

• Patients with a lack of physical integration of the upper gastrointestinal tract or with a malabsorption syndrome (e.g., patients who underwent partial or total gastric resection can participate in this clinical study, but patients equipped with a jejunostomy tube cannot participate).
• Patients with active (serious or uncontrolled) gastrointestinal bleeding.
• Patients with a history of other malignant diseases based on the date of complete recovery within 5 years prior to the initiation of treatment in this clinical study (except for in-situ cervical cancer and basal cell carcinoma).
  • Hematologic, blood chemistry, and organ functions
• History of proven congestive heart failure; angina pectoris in need of medication; evidence of transmural myocardial infarction through electrocardiogram (ECG); uncontrolled hypertension (systolic blood pressure \> 180 mmHg or diastolic blood pressure \> 100 mmHg); clinically significant heart valve disorders; and high-risk uncontrolled arrhythmia.
• Patients with dyspnoea at rest due to advanced tumors or other diseases, or who need an adjuvant oxygen therapy.
• Patients with a history of brain metastasis or clinical evidence.
• Uncontrolled serious systemic intercurrent diseases (e.g., infection or uncontrolled diabetes).
• Patients known to have HIV infectivity or active infection with HBV or HCV.
• Patients with hypersensitivity to the study drug.

Lab values

• Neutrophil count \< 1.5 × 109/L, or platelet count \< 100 × 109/L.
• Serum bilirubin\> 1.5 × upper limit of normal (ULN); or AST or ALT \> 2.5 × ULN (or \> 5 × ULN hepatic metastasis patients); or alkaline phosphatase \> 2.5 × ULN (or \> 5 × ULN hepatic metastasis patients, or \> 10 × ULN hepatic metastasis-free bone metastasis patients); or, albumin \< 2.5 g/dL.
• Creatinine clearance \< 60 mL/min. However, creatinine clearance is first calculated using the Cockroft-Gault formula, and if the value is \< 60ml/min, a 24hr urine collection test is carried out. Subject enrollment is possible only when creatinine clearance is ≥ 60mL/min.
  • Other investigational product-associated exclusion criteria
• Baseline left ventricular ejection fraction (LVEF) \< 50% (measured with echocardiogram or MUGA).

Other

• Patients with Clinically significant hypoacusis
• Patients known to show dihydropyrimidine dehydrogenase (DPD) deficiency. General exclusion criteria
• Females who are pregnant or are breast-feeding.
• Fertile males and females who are unwilling to use effective contraceptive methods.

• Patients with inoperable, locally-advanced or recurrent and/or metastatic gastric adenocarcinoma or gastroesophageal junction adenocarcinoma who are not eligible for curative therapy and are histologically diagnosed.
• Diseases measurable according to Response Evaluation Criteria in Solid Tumors (RECIST1.1) using imaging technique (CT or MRI).
• Tissue HER2-negative tumors (primary or metastatic tumors) defined as IHC2+ and FISH- or IHC 0 or 1+ according to gastric cancer assessment system for HER2 (see Annex 12.5).
• ECOG Performance status 0, 1 or 2 (see Annex 12.1).
• Survival for at least 3 months should be possible.
• Appropriate bone marrow, renal, and hepatic functions. General inclusion criteria
• Males or females aged 19 years.
• Patients should sign the informed consent form (ICF).