The aim of the study is to assess the safety and tolerability of SHR6390 combined with pyrotinib in the patients with Her-2 positive advanced gastric cancer.

Inclusion Criteria:

• Patients definitely diagnosed by pathology as Her2 positive stage III/IV gastric cancer
• 18-75 years old, ECOG PS:0-1,Life expectancy of more than12 weeks;
• Patients treated with systematic treatment to metastatic disease then experienced progressive disease
• Patients with at least one evaluable or measurable disease per RECIST v1.1
• Main organs function is normal;
• Patients should be voluntary and sign the informed consent before taking part in the study;

Exclusion Criteria:

• • Patients who have uncontrollable effusion with clinical symptoms such as severe pleural effusion and peritoneal effusion;

  • A variety of factors that affect oral medication (such as inability to swallow, gastrointestinal resection, chronic diarrhea, intestinal obstruction, etc.)
  • Patients who have steroid treatment for more than 30 days or need long-term steroid treatment;
  • Patients who had previously received chemotherapy，radiotherapy, hormonotherapy,surgery,targeted therapy(including Trastuzumab) within 2 weeks ;patients who had previously received nitrosourea or Mitomycin with 6 weeks;
  • Previous treatment-related adverse events did not recover to less than 2 levels except hair loss or other conditions that did not affect the enrollment according to investigators;
  • Patients who have participated in other anticancer drug clinical trials within 4 weeks except that trial is observational or at follow up stage;
  • Patients who have uncontrollable hypomagnesemia or hypokalemia;
  • Patients with untreated or symptomatic brain metastasis;
  • Patients with malignant tumors within 5 years, except for basal cell carcinoma,squamous skin cancer and cervical carcinoma in situ;
  • Patients who are being treated with any other anticancer strategies;
  • Patients with allergic constitution or being allergic to any element in the study drugs;
  • Patients with definite gastrointestinal bleeding tendency, including: active ulcer lesions with OB(++);melena or haematemesis history within 2 months; patients with OB(+) but without tumor resection need gastroscopy. If there is active bleeding, it's not suitable for this trial;
  • Patients with active infection, including tuberculosis;
  • Patients with immunodeficiency, including HIV positive or other acquired, congenital immunodeficiency disease, or organ transplant history;
  • Patients who have had severe cardiac disease within six months, including acute coronary syndrome, arrhythmias that require medication or with clinical significance, or need continuous medication that may cause QT extension, acute myocardial infarction,heart failure,and any other condition that is not suitable for this experiment according to the investigators;
  • Patients who are pregnant or breast feeding;
  • Patients who don't agree on contraception; Patients with concomitant diseases which could seriously endanger themselves or those who won't complete the study according to investigators such as hypertension, severe diabetes and thyroid diseases;
  • Patients with bad addiction such as excessive drinking or smoking;
  • Patients with definite mental disorder, including epilepsy and dementia.