Personalized Tumor Neoantigen MRNA Therapy for Advanced Pancreatic Cancer.

Phase 1

Not yet recruiting

• Conditions: Pancreatic Cancer Metastatic; Pancreatic Cancer Non-resectable
• Interventions: Biological: individualized anti-tumor new antigen iNeo-Vac-R01 injection; Drug: mFOLFIRINOX Treatment Regimen; Drug: Sintilimab injection

• Registration Number: NCT06888648
• Lead Sponsor: Zhejiang University

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Status Verified: 2025-03
• Study First Submitted: 2025-03-15
• Study First Submitted QC: 2025-03-15
• Last Update Submitted: 2025-03-15
• Study First Posted: 2025-03-21
• Last Update Posted: 2025-03-21
• Study Start: 2025-04-01
• Primary Completion: 2027-04-01
• Study Completion: 2028-04-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 30

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Arm A	individualized anti-tumor new antigen iNeo-Vac-R01 injection	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.
Arm A	mFOLFIRINOX Treatment Regimen	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.
Arm A	Sintilimab injection	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.

Primary Outcome Measures

Name	Time	Method
Occurence and frequence of AE and SAE	Up to 2 years	Occurence and frequence of Adverse Event (AE) and Serious Adverse Event (SAE) (NCI CTCAE 5.0)

Secondary Outcome Measures

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

Trial Locations

Locations (1)

First Affiliated Hospital of Zhejiang University Schlool of Medicine; 🇨🇳 Hangzhou, Zhejiang, China