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

NCT06888674 | Not Yet Recruiting Phase 1

• 1 other identifier: CISPD-11
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

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.

Conditions

Pancreatic Cancer Resectable

Outcome Measures

Primary Outcomes (1)

• Occurence and frequence of AE and SAE

  Occurence and frequence of Adverse Event (AE) and Serious Adverse Event (SAE) (NCI CTCAE 5.0)

  Up to 2 years

Secondary Outcomes (10)

• 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

Study Arms (2)

Arm A (Chemotherapy-Tolerant Patients)

EXPERIMENTAL

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.

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

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

EXPERIMENTAL

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).

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

Interventions

individualized anti-tumor new antigen iNeo-Vac-R01 injection BIOLOGICAL

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.

Arm A (Chemotherapy-Tolerant Patients); Arm B (Chemotherapy-Intolerant or Chemotherapy-Declined Patients)

Gemcitabine + Capecitabine DRUG

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.

Arm A (Chemotherapy-Tolerant Patients)

Sintilimab injection DRUG

Sintilimab Injection, 200mg, intravenous infusion, every 3 weeks

Arm A (Chemotherapy-Tolerant Patients); Arm B (Chemotherapy-Intolerant or Chemotherapy-Declined Patients)

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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;

You may not qualify if:

• 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:

Sponsors & Collaborators

• Zhejiang University: lead
• Hangzhou Neoantigen Therapeutics Co., Ltd.: collaborator

Study Sites (1)

First Affiliated Hospital of Zhejiang University Schlool of Medicine

Hangzhou, Zhejiang, China

Location

MeSH Terms

Interventions

Gemcitabine; Capecitabine; sintilimab

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Central Study Contacts

Tingbo Liang, MD., PhD.

CONTACT

+8619941463683; liangtingbo@zju.edu.cn

Yiwen Chen, MD.

CONTACT

+8615088682641; yiwenchen0705@126.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: The chairman of the First Affiliated Hospital of Zhejiang University School of Medicine

Study Record Dates

• First Submitted: March 15, 2025
• First Posted: March 21, 2025
• Study Start: April 1, 2025
• Primary Completion (Estimated): April 1, 2027
• Study Completion (Estimated): April 1, 2029
• Last Updated: March 21, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)