pd-1 antibody in ebv positive metastatic gastric cancer patients.

Conditions: Gastric Cancer Stage IV; EBV

Summary: ebv positive tumor accounts for 8-9% of all gastric cancer (gc) patients. pd-1 antibody has been proved as third line therapy for pd-l1 positive gastric cancer. previous studies showed that ebv(+) tumors exhibit high response to pd-1 antibody. in this phase ii study, we will investigate the efficacy and safety of pd-1 antibody in ebv positive metastatic gc patients.

ebv positive metastatic gc patients who failed to standard chemotherapy will receive therapy of single agent, pd-1 antibody, shr-1210, 200mg, every 2 weeks. the primary endpoint is response rate. secondary endpoint is progress free survival, overall survival, safety and quality of life. using the simon two-stage sample size calculation, the sample size is 19. we will collect tissue and blood sample for exploratory analysis, including pd-l1 stuatus, tumor mutation burden, et al.

Eligibility criteria:
inclusion criteria: 1. histologically confirmed recurrent/metastatic gastric adenocarcinoma; 2. eber positive; 3. failed from first-line platinum and fluorouracil based chemotherapy and second-line chemotherapy; or could not tolerate systematic chemotherapy 4. ecog performance status of 0 or 1; 5. life expectancy ≥ 12 weeks; 6. subjects must have measurable disease by ct or mri per recist 1.1 criteria; 7. can provide either a newly obtained or archival tumor tissue sample; 8. adequate laboratory parameters during the screening period as evidenced by the following: absolute neutrophil count ≥ 1.5 × 10\^9/l ; platelets ≥ 90 × 10\^9/l; hemoglobin ≥ 9.0 g/dl; serum albumin ≥ 2.8g/dl; total bilirubin (tbil) ≤ 1.5 × upper limit of normal (uln), alt and ast ≤ 1.5×uln creatinine clearance≥50 ml/min; 9. female of child bearing potential, a negative urine or serum pregnancy test result within 72 h before study treatment. participants of reproductive potential must be willing to use adequate contraception for the course of the study through 60 days after the last dose of shr-1210. male subjects must be willing to use adequate contraception for the course of the study through 120 days after the last dose of shr-1210; 10. subjects must be willing to participate in the research and sign an informed consent form (icf); exclusion criteria: 1. subjects with any active autoimmune disease or history of autoimmune disease; 2. subjects having clinical symptoms of metastases to central nervous system (such as cerebral edema, requiring steroids intervention, or brain metastasis progression); 3. has a known additional malignancy within the last 5 years before study treatment with the exception of curatively treated basal cell and squamous cell carcinoma of the skin and/or curatively resected in-situ cervical cancers; 4. uncontrolled clinically significant heart disease, including but not limited to the following: (1) \> nyha ii congestive heart failure; (2) unstable angina, (3) myocardial infarction within the past 1 year; (4) clinically significant supraventricular arrhythmia or ventricular arrhythmia requirement for treatment or intervention; 5. concurrent medical condition requiring the use of cortisol (\>10mg/day prednisone or equivalent dose) or other systematic immunosuppressive medications within 14 days before the study treatment. except: inhalation or topical corticosteroids. doses \> 10 mg/day prednisone or equivalent for replacement therapy; 6. has received prior anti-cancer monoclonal antibody (mab), chemotherapy, targeted small molecule therapy within 4 weeks prior to first dosing or not recovered to ≤ctcae 1 from adverse events (except for hair loss or neurotoxic sequelae from prior platinum therapy) due to a previously administered agent. 7. palliative irradiation finished within 2 weeks; 8. active infection or an unexplained fever \> 38.5°c before two weeks of first dosing (subjects with tumor fever may be enrolled at the discretion of the investigator); 9. known human immunodeficiency virus (hiv) infection、active hepatitis b or hepatitis c; 10. currently participating or has participated in a study within 4 weeks of the first dose of study medication; 11. pregnancy or breast feeding; 12. prior therapy with a pd-1, anti-pd-ligand 1 (pd-l1) or ctla-4 agent; 13. subjects are known to have a history of psychiatric substance abuse, alcoholism, or drug addiction; 14. according to the investigator, other conditions that may lead to stop the research.

Keywords: ebv gatric cancer check point inhibitor