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

Phase II Study of PD-1 Antibody SHR-1210 in EBV Positive Metastatic Gastric Cancer Patients.

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.

Study Overview

• Status: Completed
• Conditions: Gastric Cancer Stage IV; EBV
• Intervention / Treatment: Drug: PD-1 antibody (SHR-1210)

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 Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510060
      • Cancer center of Sun Yat-sen University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response rate	The percentage of patients whose cancer shrinks or disappears after treatment	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)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-Free Survival (PFS)	PFS as measured in accordance with the Response Evaluation Criteria In Solid Tumours (RECIST) version 1.1	up to approximately 1 year
Disease Control Rate (DCR)	Based on Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1)	From first patient first visit to 6 month after last patient first visit
Overall Survival (OS)	The time from registration to death due to any cause, or censored at date last known alive.	up to approximately 2 year

Collaborators and Investigators

• Sponsor: Sun Yat-sen University
• Investigators: Principal Investigator: Rui-hua Xu, MD, PhD, Sun Yat-sen University

Publications and helpful links

General Publications

• Sun YT, Guan WL, Zhao Q, Wang DS, Lu SX, He CY, Chen SZ, Wang FH, Li YH, Zhou ZW, Xu RH, Qiu MZ. PD-1 antibody camrelizumab for Epstein-Barr virus-positive metastatic gastric cancer: a single-arm, open-label, phase 2 trial. Am J Cancer Res. 2021 Oct 15;11(10):5006-5015. eCollection 2021.

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2018
• Primary Completion (Actual): December 31, 2020
• Study Completion (Actual): December 31, 2020

Study Registration Dates

• First Submitted: November 22, 2018
• First Submitted That Met QC Criteria: November 26, 2018
• First Posted (Actual): November 28, 2018

Study Record Updates

• Last Update Posted (Actual): September 21, 2022
• Last Update Submitted That Met QC Criteria: September 16, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Keywords: EBV; Check point inhibitor; Gatric cancer
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Stomach Diseases; Stomach Neoplasms; Physiological Effects of Drugs; Immunologic Factors; Antibodies
• Other Study ID Numbers: EBVaGC-SYSUCC

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No