Tumor Neoantigen Vaccine SarVac Combined With Tumor Specific Lymphocyte Reinfusion in the Treatment of Advanced Sarcoma

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.

Study Overview

• Status: Recruiting
• Conditions: Osteosarcoma; Soft Tissue Sarcoma (STS)
• Intervention / Treatment: Biological: Neoantigen vaccine + specific lymphocytes + anti-PD1 antibody; Biological: Neoantigen vaccine + anti-PD1 antibody

Detailed Description

Soft tissue sarcoma (STS) represents a heterogeneous group of malignant tumors. The prognosis is poor with an overall survival of 12-19 months for patients with metastasis. A critical unmet medical need is to develop novel and effective therapeutic approaches to improve the survival of patients with STS, for whom limited alternative chemotherapeutic or targeting regimens are available.

In recent years, tumor immunotherapy has emerged as a promising alternative to traditional treatments like surgery, chemotherapy, and radiotherapy. This approach includes four primary categories: immune checkpoint blockade, immunomodulators, adoptive cell transfer, and tumor vaccines. Immune checkpoint inhibitors, such as PD-1/PD-L1 and CTLA-4 antibodies, have shown efficacy in treating certain cancers. Tumor vaccines, which utilize tumor antigens to stimulate specific immune responses against cancer cells, offer notable advantages. These vaccines are characterized by low toxicity, high specificity, and the ability to induce immune memory, thereby reducing the risk of recurrence. Tumor-specific lymphocytes further enhance the immune system's capacity to target and kill tumor cells directly.

This study utilizes next-generation sequencing technology and bioinformatics analysis to accurately identify personalized tumor neoantigens. By screening for neoantigens with high MHC affinity and strong immunogenicity, we develop a personalized neoantigen vaccine, SarcVac. Subsequently, these neoantigens are used in vitro to activate and expand the patient's peripheral blood lymphocytes, yielding tumor-specific lymphocytes. This clinical trial will assess the safety and tolerability of the neoantigen vaccine (SarcVac) in combination with a PD-1 antibody, with or without tumor-specific lymphocytes, in patients with advanced solid tumors. Additionally, a preliminary assessment of its efficacy will be conducted.

• Study Type: Interventional
• Enrollment (Estimated): 16
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Zhang; Phone Number: 86-020-87343192; Email: zhangxing@sysucc.org.cn

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510000
      • Recruiting
      • Sun Yat-sen University Cancer Center
      • Contact: Zhang; Phone Number: 86-020-87343192; Email: zhangxing@sysucc.org.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Before any procedures related to the research program, including screening and evaluation stage, signed informed consent.
2. Age≥18 years old, and≤70 years old ;
3. Pathologically diagnosed as solid tumors, including bone or soft tissue sarcoma, and staging for advanced or unresectable patients ;
4. Patients with first-line treatment failure ;
5. No previous tumor vaccine treatment ; no previous treatment with PD-1 antibody ;
6. According to the RECIST1.1 standard, there are measurable lesions and superficial lesions ;
7. 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 :

1. White blood cell count ≥ 3.0 × 109 / L;
2. absolute neutrophil count ( ANC ) ≥ 1.5 × 109 / L ( without GCSF support ) ;
3. absolute lymphocyte count ( ALC ) ≥ 1.0 × 109 / L;
4. platelet ( PLT ) ≥ 75 × 109 / L;
5. hemoglobin ≥ 90g / dL ( no blood transfusion in the past 7 days ) ;
6. Prothrombin time or INR ≤ 1.5x normal upper limit time, unless receiving anticoagulant therapy;
7. partial thromboplastin time ( APTT ) ≤ 1.5x normal upper limit time, unless receiving anticoagulant therapy;
8. serum creatinine ≤ 1.5 × ULN ( upper limit of normal ) ; 24-hour creatinine clearance rate ≥ 60 mL / min;
9. Aspartate Aminotransferase (AST/SGOT) ≤ 2 × ULN;
10. Alanine Aminotransferase (ALT/SGPT) ≤ 2 × ULN;
11. 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.

Exclusion Criteria:

• 1. Before any procedures related to the research program, including screening and evaluation stage, signed informed consent.

  2. Age≥18 years old, and≤70 years old ; 3. Pathologically diagnosed as solid tumors, including bone or soft tissue sarcoma, and staging for advanced or unresectable patients ; 4. Patients with first-line treatment failure ; 5. No previous tumor vaccine treatment ; no previous treatment with PD-1 antibody ; 6. According to the RECIST1.1 standard, there are measurable lesions and superficial lesions ; 7. 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 :

1. White blood cell count ≥ 3.0 × 109 / L;
2. absolute neutrophil count ( ANC ) ≥ 1.5 × 109 / L ( without GCSF support ) ;
3. absolute lymphocyte count ( ALC ) ≥ 1.0 × 109 / L;
4. platelet ( PLT ) ≥ 75 × 109 / L;
5. hemoglobin ≥ 90g / dL ( no blood transfusion in the past 7 days ) ;
6. Prothrombin time or INR ≤ 1.5x normal upper limit time, unless receiving anticoagulant therapy;
7. partial thromboplastin time ( APTT ) ≤ 1.5x normal upper limit time, unless receiving anticoagulant therapy;
8. serum creatinine ≤ 1.5 × ULN ( upper limit of normal ) ; 24-hour creatinine clearance rate ≥ 60 mL / min;
9. Aspartate Aminotransferase (AST/SGOT) ≤ 2 × ULN;
10. Alanine Aminotransferase (ALT/SGPT) ≤ 2 × ULN;
11. 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Drug delivery mode 1; Neoantigen Vaccine Injection: Each subject receives injections of vaccine components determined from prior in vitro experiments throughout the treatment course. The SarcVac peptide vaccine, mixed with an adjuvant (PolyI:C) in 0.5 ml of saline, is administered subcutaneously in the inguinal region on days 1, 3, 7, 15, 30, 65, and 86 from treatment initiation.; Tumor-Specific Lymphocyte Infusion: Throughout the treatment course, each subject receives tumor-specific lymphocyte infusions.; Antibody Therapy: Subjects receive anti-PD-1 antibody (Sintilimab) via intravenous infusion throughout the treatment period.	Biological: Neoantigen vaccine + specific lymphocytes + anti-PD1 antibody; Neoantigen vaccine+ specific lymphocytes + anti-PD1 antibody
Experimental: Drug delivery mode 2; Neoantigen Vaccine Injection: Each subject receives injections of vaccine components determined from prior in vitro experiments throughout the treatment course. The SarcVac peptide vaccine, mixed with an adjuvant (PolyI:C) in 0.5 ml of saline, is administered subcutaneously in the inguinal region on days 1, 3, 7, 15, 30, 65, and 86 from treatment initiation.; Antibody Therapy: Subjects receive anti-PD-1 antibody (Sintilimab) via intravenous infusion throughout the treatment period.	Biological: Neoantigen vaccine + anti-PD1 antibody; Neoantigen vaccine + anti-PD1 antibody

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence and severity of adverse events	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.	120 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ORR	The secondary objectives are to assess the preliminary efficacy of SarcVac combined with a PD-1 antibody, with or without tumor-specific lymphocytes, and to evaluate whether the vaccine's efficacy demonstrates dose dependency.	270 days
DCR	The secondary objectives are to assess the preliminary efficacy of SarcVac combined with a PD-1 antibody, with or without tumor-specific lymphocytes, and to evaluate whether the vaccine's efficacy demonstrates dose dependency.	270 days

Collaborators and Investigators

• Sponsor: Sun Yat-sen University

Study record dates

Study Major Dates

• Study Start (Actual): September 3, 2024
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): June 30, 2027

Study Registration Dates

• First Submitted: June 10, 2026
• First Submitted That Met QC Criteria: June 12, 2026
• First Posted (Actual): June 15, 2026

Study Record Updates

• Last Update Posted (Actual): June 15, 2026
• Last Update Submitted That Met QC Criteria: June 12, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Neoplasms, Connective and Soft Tissue; Neoplasms, Bone Tissue; Neoplasms, Connective Tissue; Sarcoma; Osteosarcoma
• Other Study ID Numbers: SunYat-senU-T2023-002

Drug and device information, study documents

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