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PD-1 Antibody in EBV Positive Metastatic Gastric Cancer Patients.

Phase 2
Completed
Conditions
EBV
Gastric Cancer Stage IV
Interventions
Drug: PD-1 antibody (SHR-1210)
Registration Number
NCT03755440
Lead Sponsor
Sun Yat-sen University
Brief 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.

Detailed Description

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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
6
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;

  7. 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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
PD-1 antibodyPD-1 antibody (SHR-1210)SHR-1210, 200mg, ivdrip, d1, every two weeks.
Primary Outcome Measures
NameTimeMethod
Response rateFrom first patient first visit to 6 month after last patient first visit ] Based on Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1)

The percentage of patients whose cancer shrinks or disappears after treatment

Secondary Outcome Measures
NameTimeMethod
Progression-Free Survival (PFS)up to approximately 1 year

PFS as measured in accordance with the Response Evaluation Criteria In Solid Tumours (RECIST) version 1.1

Overall Survival (OS)up to approximately 2 year

The time from registration to death due to any cause, or censored at date last known alive.

Disease Control Rate (DCR)From first patient first visit to 6 month after last patient first visit

Based on Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1)

Trial Locations

Locations (1)

Cancer center of Sun Yat-sen University

🇨🇳

Guangzhou, Guangdong, China

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