Clinical Study to Evaluate the Safety and Efficacy of Personalized Tumor Neoantigen MRNA Therapy Combined with PD-1 Antibody and Chemotherapy As Adjuvant Treatment for Postoperative Pancreatic Cancer.
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- Occurence and frequence of AE and SAE
研究概览
简要总结
This study is a single-center, open-label clinical study to evaluate the feasibility and safety of personalized tumor neoantigen mRNA therapy (iNeo-Vac-R01) in combination with PD-1 antibody and standard chemotherapy regimen as adjuvant treatment for postoperative resectable pancreatic cancer.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Pre-Screening Phase Inclusion Criteria (for Radical Surgery and Vaccine Preparation):
- •Subjects meeting all of the following criteria will enter the pre-screening phase for radical surgery and vaccine preparation:
- •Voluntarily sign the informed consent form (ICF);
- •Age ≥18 years, regardless of gender;
- •Diagnosed with resectable pancreatic cancer as assessed per the 2024 NCCN Clinical Practice Guidelines and willing to undergo radical surgery;
- •ECOG Performance Status score of 0 or 1;
- •Ability to obtain sufficient fresh tumor tissue samples for whole-exome sequencing (WES) and transcriptome sequencing analysis;
- •Normal function of major organs (heart, liver, kidneys):
- •Liver function: Total bilirubin ≤1.5×ULN; ALT/AST ≤2.5×ULN;
- •Renal function: Serum creatinine ≤1.5×ULN or creatinine clearance ≥60 mL/min (Cockcroft-Gault formula);
- •Cardiac function: LVEF ≥50% by echocardiography;
- •Contraception agreement: Fertile males and females of childbearing potential must agree to use effective contraception from signing the ICF until 6 months after the last dose of study treatment. Females of childbearing potential include premenopausal women and women ≤2 years postmenopausal;
- •Ability to comply with the study protocol and follow-up procedures.
- •Formal Screening Phase Inclusion Criteria (for Study Treatment Initiation):
- •Subjects meeting all of the following criteria will enter the formal screening phase for study treatment:
- •Voluntarily sign the informed consent form (ICF);
- •Age ≥18 years, regardless of gender;
- •Histologically confirmed pancreatic ductal adenocarcinoma (PDAC) post-surgery;
- •Completion of radical resection (R0 or R1) with no evidence of metastatic disease, malignant ascites, or pleural effusion on imaging 4-12 weeks postoperatively;
- •ECOG Performance Status score:Cohort A: 0 or 1;Cohort B: 0-2;
- •Normal function of major organs (heart, liver, kidneys):
- •Contraception agreement: Same as pre-screening criteria;
- •Ability to comply with the study protocol and follow-up procedures.
排除标准
- •Subjects meeting any of the following criteria will be excluded from the study:
- •Serum CA 19-9 level >180 U/mL within 21 days prior to initiating standard postoperative adjuvant therapy;
- •History of bone marrow transplantation, allogeneic organ transplantation, or allogeneic hematopoietic stem cell transplantation;
- •Concurrent immunosuppressive therapy, defined as regular use of immunosuppressive agents within 4 weeks prior to screening or during the study, including but not limited to:
- •Severe asthma requiring systemic corticosteroids (≥10 mg/day prednisone equivalent);
- •Active autoimmune disease or immunodeficiency (e.g., rheumatoid arthritis, systemic lupus erythematosus);
- •History of primary immunodeficiency;
- •Exceptions: Type 1 diabetes, autoimmune hypothyroidism managed with hormone replacement, vitiligo, or psoriasis not requiring systemic therapy;
- •Active bacterial/fungal infections requiring systemic treatment, or active/latent tuberculosis (confirmed by interferon-gamma release assay or tuberculin skin test);
- •Active viral infections:
- •HIV antibody-positive;
- •Syphilis (TP antibody-positive with RPR/TRUST confirmation);
- •Active hepatitis C (HCV RNA-positive);
- •Active hepatitis B (HBsAg-positive and HBV DNA ≥2000 IU/mL);
- •Acute viral infections:
- •Herpesvirus infection (unless resolved with crusting >4 weeks prior);
- •Respiratory viral infection (unless resolved >4 weeks prior);
- •Uncontrolled comorbidities:
- •Symptomatic congestive heart failure (NYHA Class III/IV);
- •Unstable angina or arrhythmia requiring treatment;
- •Severe coronary/cerebrovascular disease (e.g., myocardial infarction within 6 months);
- •Other conditions deemed exclusionary by the investigator;
- •History of drug abuse, psychiatric disorders, or psychosocial factors impairing informed consent or protocol compliance;
- •History of severe hypersensitivity to vaccines, biologics, or any component of the study drug;
- •Pregnancy or lactation;
- •Other conditions judged by the investigator to preclude safe participation.
研究组 & 干预措施
Arm A (Chemotherapy-Tolerant Patients)
Postoperative evaluation will be conducted within 4-12 weeks after surgery, and patients without recurrence will be enrolled. For patients who are chemotherapy-tolerant (evaluated by investigators), adjuvant therapy is to commence within 6-12 weeks postoperatively, with the first day of treatment (D1) defined as the date of initial postoperative intervention. Postoperative treatment follows the:
1.Gemcitabine + Capecitabine (GC) regimen+ Sintilimab: Gemcitabine: 1000 mg/m², intravenously on D1 and D8;Capecitabine: 1650-2000 mg/(m²·day), divided into two daily oral doses from D1 to D14；Sintilimab (200 mg); Q3W for 8 cycles.2.Personalized mRNA injection (100 μg subcutaneously, Q3W) administered from D22±3.
On Day 43 ±3 days: The second efficacy assessment will be performed. Patients without disease progression will continue treatment. Patients with disease progression will transition to a second-line chemotherapy regimen (decided by investigators) combined with mRNA and Sintilimab.
干预措施: individualized anti-tumor new antigen iNeo-Vac-R01 injection (Biological)
Arm A (Chemotherapy-Tolerant Patients)
Postoperative evaluation will be conducted within 4-12 weeks after surgery, and patients without recurrence will be enrolled. For patients who are chemotherapy-tolerant (evaluated by investigators), adjuvant therapy is to commence within 6-12 weeks postoperatively, with the first day of treatment (D1) defined as the date of initial postoperative intervention. Postoperative treatment follows the:
1.Gemcitabine + Capecitabine (GC) regimen+ Sintilimab: Gemcitabine: 1000 mg/m², intravenously on D1 and D8;Capecitabine: 1650-2000 mg/(m²·day), divided into two daily oral doses from D1 to D14；Sintilimab (200 mg); Q3W for 8 cycles.2.Personalized mRNA injection (100 μg subcutaneously, Q3W) administered from D22±3.
On Day 43 ±3 days: The second efficacy assessment will be performed. Patients without disease progression will continue treatment. Patients with disease progression will transition to a second-line chemotherapy regimen (decided by investigators) combined with mRNA and Sintilimab.
干预措施: Gemcitabine + Capecitabine (Drug)
Arm A (Chemotherapy-Tolerant Patients)
Postoperative evaluation will be conducted within 4-12 weeks after surgery, and patients without recurrence will be enrolled. For patients who are chemotherapy-tolerant (evaluated by investigators), adjuvant therapy is to commence within 6-12 weeks postoperatively, with the first day of treatment (D1) defined as the date of initial postoperative intervention. Postoperative treatment follows the:
1.Gemcitabine + Capecitabine (GC) regimen+ Sintilimab: Gemcitabine: 1000 mg/m², intravenously on D1 and D8;Capecitabine: 1650-2000 mg/(m²·day), divided into two daily oral doses from D1 to D14；Sintilimab (200 mg); Q3W for 8 cycles.2.Personalized mRNA injection (100 μg subcutaneously, Q3W) administered from D22±3.
On Day 43 ±3 days: The second efficacy assessment will be performed. Patients without disease progression will continue treatment. Patients with disease progression will transition to a second-line chemotherapy regimen (decided by investigators) combined with mRNA and Sintilimab.
干预措施: Sintilimab injection (Drug)
Arm B (Chemotherapy-Intolerant or Chemotherapy-Declined Patients)
Postoperative evaluation will be conducted within 4-12 weeks after surgery, and patients without recurrence will be enrolled. For patients who are Chemotherapy-Intolerant or Chemotherapy-Declined, postoperative treatment consists of Sintilimab (200 mg via intravenous infusion) administered Q3W for 8 cycles. On Day 22 ± 3 days, patients will initiate treatment with personalized mRNA injection at a dose of 100 μg administered subcutaneously Q3W, for a maximum of 9 doses.
On Day 43 ±3 days: The second efficacy assessment will be performed. Patients without disease progression will continue treatment. Patients with disease progression will transition to a second-line chemotherapy regimen (decided by investigators) combined with personalized mRNA injection (100 μg subcutaneously,Q3W) and Sintilimab (200 mg via intravenous infusion, Q3W).
干预措施: individualized anti-tumor new antigen iNeo-Vac-R01 injection (Biological)
Arm B (Chemotherapy-Intolerant or Chemotherapy-Declined Patients)
Postoperative evaluation will be conducted within 4-12 weeks after surgery, and patients without recurrence will be enrolled. For patients who are Chemotherapy-Intolerant or Chemotherapy-Declined, postoperative treatment consists of Sintilimab (200 mg via intravenous infusion) administered Q3W for 8 cycles. On Day 22 ± 3 days, patients will initiate treatment with personalized mRNA injection at a dose of 100 μg administered subcutaneously Q3W, for a maximum of 9 doses.
On Day 43 ±3 days: The second efficacy assessment will be performed. Patients without disease progression will continue treatment. Patients with disease progression will transition to a second-line chemotherapy regimen (decided by investigators) combined with personalized mRNA injection (100 μg subcutaneously,Q3W) and Sintilimab (200 mg via intravenous infusion, Q3W).
干预措施: Sintilimab injection (Drug)
结局指标
主要结局
Occurence and frequence of AE and SAE
时间窗: Up to 2 years
Occurence and frequence of Adverse Event (AE) and Serious Adverse Event (SAE) (NCI CTCAE 5.0)
次要结局
- Recurrence-Free Survival (RFS)(Up to 2 years)
- Recurrence-Free Survival Rate (RFS%)(Up to 3 years)
- Overall Survival (OS)(Up to 4 years)
- Overall Survival Rate (OS%)(Up to 3 years)
- Efficacy Evaluation Metrics for Patients with Recurrence: Objective Response Rate (ORR)(Up to 3 years)
- Efficacy Evaluation Metrics for Patients with Recurrence: Disease Control Rate (DCR)(Up to 3 years)
- Efficacy Evaluation Metrics for Patients with Recurrence: Progression-Free Survival (PFS)(Up to 3 years)
- Efficacy Evaluation Metrics for Patients with Recurrence: Progression-Free Survival Rate (PFS%)(Up to 3 years)
- Efficacy Evaluation Metrics for Patients with Recurrence: Overall Survival (OS)(Up to 4 years)
- Efficacy Evaluation Metrics for Patients with Recurrence: Overall Survival Rate (OS%)(Up to 3 years)
研究者
TingBo Liang
The chairman of the First Affiliated Hospital of Zhejiang University School of Medicine
First Affiliated Hospital of Zhejiang University