A Prospective, Single-center, Double-arm, Phase I Clinical Trial of Tumor Neoantigen Vaccine SarVac Combined With Tumor-specific Lymphocyte Reinfusion in the Treatment of Patients With Advanced or Unresectable Sarcoma-based Solid Tumors Who Failed Standard Treatment.
The primary objective of this trial is to evaluate the safety and tolerability of the tumor neoantigen vaccine (SarcVac) in combination with a PD-1 antibody, with or without tumor-specific lymphocytes, in patients with advanced bone and soft tissue sarcoma who have failed first-line treatment. The secondary objectives are to assess the preliminary efficacy of SarcVac combined with a PD-1 antibody, with or without tumor-specific lymphocytes, in these patients and to evaluate whether the vaccine's efficacy demonstrates dose dependency.
• Before any procedures related to the research program, including screening and evaluation stage, signed informed consent.
• Age≥18 years old, and≤70 years old ;
• Pathologically diagnosed as solid tumors, including bone or soft tissue sarcoma, and staging for advanced or unresectable patients ;
• Patients with first-line treatment failure ;
• No previous tumor vaccine treatment ; no previous treatment with PD-1 antibody ;
• According to the RECIST1.1 standard, there are measurable lesions and superficial lesions ;
• The following three screening indicators should be met in the test screening period:
‣ （1）The available tumor tissue samples ( paraffin sections and fresh surgical specimens ) were used for subsequent whole exome and transcriptome sequencing analysis and primary cell culture to obtain tumor neoantigen-related mutation sequence information and gene expression.
‣ ( 2 ) Available peripheral blood samples; ( 3 ) Tumor new antigen prediction analysis and in vitro laboratory testing; 8. ECOG score 0-1 ( see Appendix ) and expected survival time greater than 6 months ; 9. Patients were not allowed to use anti-tumor drugs and radiotherapy within 4 weeks before vaccination; 10. Patients with brain metastasis who were stable for at least one month after treatment can be included; 11. echocardiography showed left ventricular ejection fraction ≥ 50 %; 12. The results of laboratory tests should meet at least the following indicators :
• White blood cell count ≥ 3.0 × 109 / L;
• absolute neutrophil count ( ANC ) ≥ 1.5 × 109 / L ( without GCSF support ) ;
• absolute lymphocyte count ( ALC ) ≥ 1.0 × 109 / L;
• platelet ( PLT ) ≥ 75 × 109 / L;
• hemoglobin ≥ 90g / dL ( no blood transfusion in the past 7 days ) ;
• Prothrombin time or INR ≤ 1.5x normal upper limit time, unless receiving anticoagulant therapy;
• partial thromboplastin time ( APTT ) ≤ 1.5x normal upper limit time, unless receiving anticoagulant therapy;
• serum creatinine ≤ 1.5 × ULN ( upper limit of normal ) ; 24-hour creatinine clearance rate ≥ 60 mL / min;
• Aspartate Aminotransferase (AST/SGOT) ≤ 2 × ULN;
⁃ Alanine Aminotransferase (ALT/SGPT) ≤ 2 × ULN;
⁃ total bilirubin ( TBIL ) ≤ 1 × ULN 13. Females with fertility were negative in pregnancy test before treatment ; consent must be given to the use of contraception or the prohibition of same-sex or opposite-sex sexual activity during treatment; 14. During the whole experiment, we can regularly go to the research institutions to carry out relevant testing, evaluation and management.