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

Zhejiang University

Status and phase: Not yet enrolling; Phase 2; Phase 1

Conditions: Pancreatic Cancer Resectable

Treatments: Drug: Sintilimab injection; Biological: individualized anti-tumor new antigen iNeo-Vac-R01 injection; Drug: Gemcitabine + Capecitabine

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT06888674

CISPD-11

Details and patient eligibility

About

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.

Enrollment: 60 estimated patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Prevention

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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60 participants in 2 patient groups

Arm A (Chemotherapy-Tolerant Patients)

Experimental group

Description:

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.

Treatment:

Drug: Gemcitabine + Capecitabine

Drug: Sintilimab injection

Biological: individualized anti-tumor new antigen iNeo-Vac-R01 injection

Arm B (Chemotherapy-Intolerant or Chemotherapy-Declined Patients)

Experimental group

Description:

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).

Treatment:

Drug: Sintilimab injection

Biological: individualized anti-tumor new antigen iNeo-Vac-R01 injection