Clinical trial NCT06888674: Personalized Tumor Neoantigen MRNA Therapy Adjuvant Treatment for Postoperative Pancreatic Cancer.
Official title: 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.
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Pancreatic Cancer Resectable
Lead sponsor: Zhejiang University
Sponsor class: OTHER
Collaborators: name: Hangzhou Neoantigen Therapeutics Co., Ltd.
First posted: 2025-03-21
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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.


Eligibility criteria: Inclusion Criteria:

1. 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.
2. 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.

Exclusion Criteria:

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:

  1. Severe asthma requiring systemic corticosteroids (≥10 mg/day prednisone equivalent);
  2. Active autoimmune disease or immunodeficiency (e.g., rheumatoid arthritis, systemic lupus erythematosus);
  3. History of primary immunodeficiency;
  4. 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:

  1. HIV antibody-positive;
  2. Syphilis (TP antibody-positive with RPR/TRUST confirmation);
  3. Active hepatitis C (HCV RNA-positive);
  4. Active hepatitis B (HBsAg-positive and HBV DNA ≥2000 IU/mL);
* Acute viral infections:

  1. Herpesvirus infection (unless resolved with crusting \>4 weeks prior);
  2. Respiratory viral infection (unless resolved \>4 weeks prior);
* Uncontrolled comorbidities:

  1. Symptomatic congestive heart failure (NYHA Class III/IV);
  2. Unstable angina or arrhythmia requiring treatment;
  3. Severe coronary/cerebrovascular disease (e.g., myocardial infarction within 6 months);
  4. 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.

Primary outcomes:
measure: Occurence and frequence of AE and SAE
timeFrame: Up to 2 years
Secondary outcomes:
measure: Recurrence-Free Survival (RFS)
timeFrame: Up to 2 years
measure: Recurrence-Free Survival Rate (RFS%)
timeFrame: Up to 3 years
measure: Overall Survival (OS)
timeFrame: Up to 4 years
measure: Overall Survival Rate (OS%)
timeFrame: Up to 3 years
measure: Efficacy Evaluation Metrics for Patients with Recurrence: Objective Response Rate (ORR)
timeFrame: Up to 3 years
measure: Efficacy Evaluation Metrics for Patients with Recurrence: Disease Control Rate (DCR)
timeFrame: Up to 3 years
measure: Efficacy Evaluation Metrics for Patients with Recurrence: Progression-Free Survival (PFS)
timeFrame: Up to 3 years
measure: Efficacy Evaluation Metrics for Patients with Recurrence: Progression-Free Survival Rate (PFS%)
timeFrame: Up to 3 years
measure: Efficacy Evaluation Metrics for Patients with Recurrence: Overall Survival (OS)
timeFrame: Up to 4 years
measure: Efficacy Evaluation Metrics for Patients with Recurrence: Overall Survival Rate (OS%)
timeFrame: Up to 3 years
Other outcomes:
Locations:
city: Hangzhou
country: China
facility: First Affiliated Hospital of Zhejiang University Schlool of Medicine
state: Zhejiang
Study officials:
References: