PD-1 Antibody in EBV Positive Metastatic Gastric Cancer Patients.
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: PD-1 antibody SHR-1210, 200mg, ivdrip, d1, every two weeks. |
Drug: PD-1 antibody (SHR-1210)
PD-1 antibody (SHR-1210), 200mg, ivdrip, every 2 weeks.
|
Outcome Measures
Primary Outcome Measures
- Response rate [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)]
The percentage of patients whose cancer shrinks or disappears after treatment
Secondary Outcome Measures
- 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)
Eligibility Criteria
Criteria
Inclusion Criteria:
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Histologically confirmed Recurrent/Metastatic gastric adenocarcinoma;
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EBER positive;
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Failed from first-line platinum and fluorouracil based chemotherapy and second-line chemotherapy; or could not tolerate systematic chemotherapy
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ECOG performance status of 0 or 1;
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Life expectancy ≥ 12 weeks;
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Subjects must have measurable disease by CT or MRI per RECIST 1.1 criteria;
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Can provide either a newly obtained or archival tumor tissue sample;
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Adequate laboratory parameters during the screening period as evidenced by the following:
Absolute neutrophil count ≥ 1.5 × 109/L ; Platelets ≥ 90 × 109/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;
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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;
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Subjects must be willing to participate in the research and sign an informed consent form (ICF);
Exclusion Criteria:
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Subjects with any active autoimmune disease or history of autoimmune disease;
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Subjects having clinical symptoms of metastases to central nervous system (such as cerebral edema, requiring steroids intervention, or brain metastasis progression);
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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;
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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;
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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;
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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;
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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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Cancer center of Sun Yat-sen University | Guangzhou | Guangdong | China | 510060 |
Sponsors and Collaborators
- Sun Yat-sen University
Investigators
- Principal Investigator: Rui-Hua Xu, MD, PhD, Sun Yat-sen University
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- EBVaGC-SYSUCC