Personalized Tumor Neoantigen MRNA Therapy for Advanced Pancreatic Cancer.

Clinical Study to Evaluate the Safety and Efficacy of Personalized Tumor Neoantigen MRNA Therapy in Combination with PD-1 Antibody and Chemotherapy for Advanced Pancreatic Cancer.

This study is a single-arm phase I/II clinical study to evaluate the effectiveness of evaluate the feasibility and safety of personalized tumor neoantigen mRNA therapy (iNeo-Vac-R01) in combination with PD-1 antibody and standard chemotherapy regimens for the treatment of patients with advanced pancreatic cancer.

Study Overview

• Status: Not yet recruiting
• Conditions: Pancreatic Cancer Metastatic; Pancreatic Cancer Non-resectable
• Intervention / Treatment: Drug: Sintilimab injection; Biological: individualized anti-tumor new antigen iNeo-Vac-R01 injection; Drug: mFOLFIRINOX Treatment Regimen

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Tingbo Liang, MD., PhD.; Phone Number: +8619941463683; Email: liangtingbo@zju.edu.cn
• Study Contact Backup: Name: Yiwen Chen, MD.; Phone Number: +8615088682641; Email: yiwenchen0705@126.com

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China, 31000
      • First Affiliated Hospital of Zhejiang University Schlool of Medicine
      • Contact: Yiwen Chen, MD.; Phone Number: +8615088682641; Email: yiwenchen0705@126.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

(1) Subjects who meet all the following entry criteria enter the pre-screening phase of the study:

1. Voluntary signing of the informed consent form;
2. Age: 18 and 75 years old, male or female;
3. Evaluation as metastatic pancreatic cancer or postoperative recurrence according to the 2024 NCCN guidelines;
4. No systemic treatment, or disease progression with gemcitabine-based first-line chemotherapy.
5. An Eastern Cooperative Oncology Group (ECOG) physical fitness status score of 0 or 1;
6. According to the efficacy evaluation criteria for solid tumors (RECIST 1.1);
7. Can obtain sufficient fresh tumor tissue samples for exome and transcriptome sequencing analysis;
8. Main organ function of heart, liver and kidney is normal:
9. Ferproductive men and women of childbearing age agree to take effective contraception from the date to the last dose of test drug; women of childbearing age included premenopause and women within 2 years after menopause;
10. Ability to follow the study protocol and follow-up procedures.

(2) Subjects who meet all the following enrollment criteria enter the formal screening stage of the study and enter the study medication process:

1. Voluntary signing of the informed consent form;
2. Age: 18 and 75 years old, male or female;
3. Pancreatic ductal adenocarcinoma (PDAC) diagnosed by pathology (histology or cytology);
4. No systemic treatment or gemcitabine-based first-line chemotherapy.
5. An Eastern Cooperative Oncology Group (ECOG) physical fitness status score of 0 or 1;
6. Main organ function of heart, liver and kidney is normal:
7. Ferproductive men and women of childbearing age agree to take effective contraception from the date to the last dose of test drug; women of childbearing age include premenopause and women within 2 years after menopause;
8. Ability to follow the study protocol and follow-up procedures.

Exclusion Criteria:

Subjects will be excluded from this study if they meet any of the following criteria:

1. Pancreatic cancer has central nervous system metastasis or meningeal metastasis;
2. At the same time with other malignant tumors, but cured basal cell cancer, thyroid cancer, cervical dysplasia, etc., have been in the disease for more than 5 years or do not considered to be easy to relapse except;
3. History of bone marrow transplantation, allogeneic organ transplantation, or allogeneic hematopoietic stem cell transplantation;
4. Patients with immunosuppressants, that is, those who require regular use of immunosuppressants 4 weeks before the screening period and the clinical study, including but not limited to the following conditions: severe asthma, autoimmune diseases or immune deficiency, treated with immunosuppressive drugs, and known history of primary immunodeficiency; except type 1 diabetes, autoimmune-related hypothyroidism requiring hormone therapy, vitiligo and psoriasis that do not require systemic therapy;
5. Active bacterial or fungal infection identified by clinical diagnosis; a history of active TB or tuberculosis;
6. Patients with positive human immunodeficiency virus (HIV) antibody, positive treponema pallidum for syphilis (TP) antibody, active hepatitis C (positive hepatitis C virus (HCV) antibody and positive HCV RNA result), active hepatitis B;
7. Herpesvirus infection (except those who scab for more than 4 weeks); respiratory virus infection (except those who have recovered for more than 4 weeks);
8. Uncontrolled complications include but are not limited to active infection, symptomatic congestive heart failure, unstable angina, arrhythmia; severe coronary artery disease or cerebrovascular disease, or other diseases considered unacceptable by the investigator;
9. Previous history of drug abuse, clinical or psychological or social factors affecting informed consent or study implementation; a history of mental illness;
10. Patients with a history of food, drug or vaccine allergy or other potential immunotherapy allergies as considered by the Investigator.
11. Women born during pregnancy or lactation;
12. The investigator is not fit for enrollment or may not complete the trial for other reasons.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Arm A; On D1 patients start the mFOLFIRINOX every 2 weeks, and the actual number of cycles of mFOLFIRINOX will be determined by the investigators according on the patients' physical condition, disease progression, adverse effects; on the same day, started Sintilimab, 200mg, intravenous infusion, every 3 weeks; On D43 ± 3, the first efficacy assessment will be conducted. Patient with no disease progression, will continue the above treatment (mFOLFIRINOX Q2W + Sintilimab Q3W + individualized neoantigen mRNA injection Q3W); if disease progression, the patient will receive the second-line chemotherapy regimen (decided by investigators)+ Sintilimab Q3W + individualized neoantigen mRNA injection Q3W. Patients will receive efficacy assessment every 6 weeks.

Drug: Sintilimab injection; Sintilimab Injection, 200mg, intravenous infusion, every 3 weeks; Biological: individualized anti-tumor new antigen iNeo-Vac-R01 injection; The individualized anti-tumor new antigen iNeo-Vac-R01 injection was commissioned by Hangzhou Nuanjin Biotechnology 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.; Drug: mFOLFIRINOX Treatment Regimen; continuous intravenous infusion of fluorouracil 2400mg / m², for 46 hours, leucovorin 400mg / m², irinotecan 135mg / m², and oxaliplatin 68mg / m², every 2 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective reponse rate (ORR)	The proportion of patients who had tumor evaluated as PR according to RECIST1.1 criteria during the whole study	Up to 2 years
Disease control rate (DCR)	The proportion of patients who had tumor evaluated as PR or SD according to RECIST1.1 criteria during the whole study.	Up to 2 years
Progression-free survival （PFS）	The time from enrolled to disease pregression or death from any cause during the whole study.	Up to 2 years
Overall survival (OS)	The time from enrolled to death from any cause during the whole study	Up to 2 years
Progression-free survival Rate（1-Y-PFS%, 2-Y-PFS%,3-Y-PFS%）	The proportion of patients free from disease progression or death (whichever occurs first) at 12, 24, and 36 months.	Up to 3 years
Overall Survival Rate (1-Y-OS%,2-Y-OS%,3-Y-OS%)	The percentage of patients surviving at 12, 24, and 36 months.	Up to 3 years

Collaborators and Investigators

• Sponsor: Zhejiang University
• Collaborators: Hangzhou Neoantigen Therapeutics Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2025
• Primary Completion (Estimated): April 1, 2027
• Study Completion (Estimated): April 1, 2028

Study Registration Dates

• First Submitted: March 15, 2025
• First Submitted That Met QC Criteria: March 15, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 15, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Endocrine System Diseases; Neoplasms by Site; Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Endocrine Gland Neoplasms; Pancreatic Diseases; Pancreatic Neoplasms
• Other Study ID Numbers: CISPD-10

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No