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.

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.