Personalized Tumor Neoantigen MRNA Therapy Adjuvant Treatment for Postoperative Pancreatic Cancer.

Официальное название

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.

Обзор

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.

Вмешательства

• Биопрепарат individualized anti-tumor new antigen iNeo-Vac-R01 injection
  The individualized anti-tumor new antigen iNeo-Vac-R01 injection was commissioned by Hangzhou Neoantigen Therapeutics Co., Ltd., and all patients were admitted into the therapeutic intervention group. According to the results of previous non-clinical studies, the individualized mRNA injection of 100 μ g was a tolerable dose.
• Препарат Gemcitabine + Capecitabine
  Gemcitabine: 1000 mg/m², administered intravenously over 30 minutes on Day 1 and Day 8; Capecitabine: 1650-2000 mg/(m²·day), divided into two daily oral doses from Day 1 to Day 14. Treatment cycles repeat every 3 weeks for 8 cycles, with the actual number of cycles determined by the investigator based on comprehensive evaluation of the patient's physical status, disease progression, and adverse reactions.
• Препарат Sintilimab injection
  Sintilimab Injection, 200mg, intravenous infusion, every 3 weeks

Первичные конечные точки

• Occurence and frequence of AE and SAE [Срок оценки: Up to 2 years]

Вторичные конечные точки (10)

• Recurrence-Free Survival (RFS) [Срок оценки: Up to 2 years]
• Recurrence-Free Survival Rate (RFS%) [Срок оценки: Up to 3 years]
• Overall Survival (OS) [Срок оценки: Up to 4 years]
• Overall Survival Rate (OS%) [Срок оценки: Up to 3 years]
• Efficacy Evaluation Metrics for Patients with Recurrence: Objective Response Rate (ORR) [Срок оценки: Up to 3 years]
• Efficacy Evaluation Metrics for Patients with Recurrence: Disease Control Rate (DCR) [Срок оценки: Up to 3 years]
• Efficacy Evaluation Metrics for Patients with Recurrence: Progression-Free Survival (PFS) [Срок оценки: Up to 3 years]
• Efficacy Evaluation Metrics for Patients with Recurrence: Progression-Free Survival Rate (PFS%) [Срок оценки: Up to 3 years]
• Efficacy Evaluation Metrics for Patients with Recurrence: Overall Survival (OS) [Срок оценки: Up to 4 years]
• Efficacy Evaluation Metrics for Patients with Recurrence: Overall Survival Rate (OS%) [Срок оценки: Up to 3 years]

Критерии участия

Критерии включения

• 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.

Критерии исключения

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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Профилактика

Центры проведения

Китай · 1 центр

• First Affiliated Hospital of Zhejiang University Schlool of Medicine — Ханчжоу

Идентификаторы

NCT: NCT06888674 · CISPD-11

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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