Neoantigen Reactive T Cells Combined With SHR-1210 for Chinese Patients With Advanced Refractory Solid Tumors

• Status: Unknown status
• Trial end date: 2020-12-31
• Target enrollment: 0
• Participant gender: All

Summary

The purpose of this study is to see the safety and efficient of neoantigen reactive T cells (NRTs) combined with programmed cell death-1(PD-1) inhibitor（SHR-1210）in the treatment of Chinese patients with advanced refractory solid tumors.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
• Treatments: Cyclophosphamide; Fludarabine; Fludarabine phosphate; Interleukin-2

Criteria

Inclusion Criteria:

• Adult patients aged 18 to 75 years old

• Histologic or cytologic confirmation of advanced refractory solid tumors with no available curative treatment options

• At least one measurable disease: diameter ≥20mm or spiral computed tomography(CT)≥10mm; and can providing with tumor specimen (for testing the expression of PD -L1 and the infiltrating lymphocytes)

• Must be human leukocyte antigen (HLA)-A2/A24/A11 positive

• Eastern Cooperative Oncology Group(ECOG)<0-2 and expected survival time 3 months or more

• At least one new antigen can induce T cell secrete interferon - gamma (IFN - gamma) twice as normal controls during the new antigens screening

• Without anticancer treatment more than one month

• Hematology Index including: Neutrophile granulocyte greater than 1.5×10^9/L; Hemoglobin greater than 10g/dL; Platelet greater than 100×10^9/L

• Biochemical index including: Serum bilirubin not greater than 1.5x upper limit of reference range (ULN); glutamic-pyruvic transaminase（ALT） or glutamic-oxalacetic transaminase（AST） not greater than 2.5x ULN; Creatinine clearance no less than 60ml/min

• Peripheral venous channel open and no contraindications to separating lymphocytes

• Negative pregnancy test for women of childbearing potential, and patients must be willing to practice birth control during the regimen

• Provision of informed consent

• Be able to follow the research program and follow up process

Exclusion Criteria:

• Those who now are undergoing other antitumor drug therapy (including chemotherapy, systemic steroids therapy, surgery, target therapy or immune therapy);

• Prior treatment with PD-1 monoclonal antibody(mAb） or PD-L1 mAb;

• Prior malignancy active within the previous 5 years except for locally curable cancers that have been apparently cured, such as basal cell skin cancer or carcinoma in situ of the cervix;

• History with pulmonary tuberculosis, and positive tests for Acquired Immune Deficiency Syndrome(HIV),hepatitis C virus(HCV),hepatitis B virus(HBV);

• Patients with any active autoimmune disease or a documented history of autoimmune disease, or history of syndrome that required systemic steroids or immunosuppressive medications, such as hypophysitis, pneumonia, colitis, hepatitis, nephritis, hyperthyroidism or hypothyroidism; Severe, uncontrolled medical condition that would affect patients' compliance or obscure the interpretation of toxicity determination or adverse events, including active severe infection, uncontrolled diabetes, angiocardiopathy (heart failure > class II New York Heart Association(NYHA), heart block >II grade, myocardial infarction, unstable arrhythmia or unstable angina within past 6 months, cerebral infarction within past 3 months) or pulmonary disease ( interstitial pneumonia, obstructive pulmonary disease or symptomatic bronchospasm).

• Evidence with central nervous system(CNS) disease

• Pregnant or nursing

• Psychiatric medicines abuse without withdrawal, or history of psychiatric illness.

• Hypersensitivity to investigational drugs or its components.