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

NCT ID: NCT06888674

Last Updated: 2025-03-21

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-04-01
• Study Completion Date: 2029-04-01

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

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

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

Intervention Type: 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.

Gemcitabine + Capecitabine

Intervention Type: 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.

Sintilimab injection

Intervention Type: DRUG

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

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).

Group Type: EXPERIMENTAL

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

Intervention Type: 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.

Sintilimab injection

Intervention Type: DRUG

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

Interventions

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.

Intervention Type: BIOLOGICAL

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.

Intervention Type: DRUG

Sintilimab injection

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

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 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;
• 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hangzhou Neoantigen Therapeutics Co., Ltd.

INDUSTRY

Sponsor Role: collaborator

Zhejiang University

OTHER

Sponsor Role: lead

Responsible Party

TingBo Liang

The chairman of the First Affiliated Hospital of Zhejiang University School of Medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

First Affiliated Hospital of Zhejiang University Schlool of Medicine

Hangzhou, Zhejiang, China

Countries

China

Central Contacts

Tingbo Liang, MD., PhD.

Role: CONTACT

liangtingbo@zju.edu.cn

+8619941463683

Yiwen Chen, MD.

Role: CONTACT

yiwenchen0705@126.com

+8615088682641

Facility Contacts

Yiwen Chen, MD.

Role: primary

yiwenchen0705@126.com

+8615088682641

Other Identifiers

CISPD-11

Identifier Type: -

Identifier Source: org_study_id