Personalized Tumor Neoantigen MRNA Therapy for Advanced Pancreatic Cancer.

Official title

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.

Overview

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.

Interventions

• 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
• Drug Sintilimab injection
  Sintilimab Injection, 200mg, intravenous infusion, every 3 weeks

Primary outcome measures

• Occurence and frequence of AE and SAE [Time frame: Up to 2 years]

Secondary outcome measures (6)

• Objective reponse rate (ORR) [Time frame: Up to 2 years]
• Disease control rate (DCR) [Time frame: Up to 2 years]
• Progression-free survival （PFS） [Time frame: Up to 2 years]
• Overall survival (OS) [Time frame: Up to 2 years]
• Progression-free survival Rate（1-Y-PFS%, 2-Y-PFS%,3-Y-PFS%） [Time frame: Up to 3 years]
• Overall Survival Rate (1-Y-OS%,2-Y-OS%,3-Y-OS%) [Time frame: Up to 3 years]

Eligibility criteria

Inclusion criteria

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

• Voluntary signing of the informed consent form;
• Age: 18 and 75 years old, male or female;
• Evaluation as metastatic pancreatic cancer or postoperative recurrence according to the 2024 NCCN guidelines;
• No systemic treatment, or disease progression with gemcitabine-based first-line chemotherapy.
• An Eastern Cooperative Oncology Group (ECOG) physical fitness status score of 0 or 1;
• According to the efficacy evaluation criteria for solid tumors (RECIST 1.1);
• Can obtain sufficient fresh tumor tissue samples for exome and transcriptome sequencing analysis;
• Main organ function of heart, liver and kidney is normal:
• 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;
• 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:

• Voluntary signing of the informed consent form;
• Age: 18 and 75 years old, male or female;
• Pancreatic ductal adenocarcinoma (PDAC) diagnosed by pathology (histology or cytology);
• No systemic treatment or gemcitabine-based first-line chemotherapy.
• An Eastern Cooperative Oncology Group (ECOG) physical fitness status score of 0 or 1;
• Main organ function of heart, liver and kidney is normal:
• 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;
• 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:

• Pancreatic cancer has central nervous system metastasis or meningeal metastasis;
• 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;
• History of bone marrow transplantation, allogeneic organ transplantation, or allogeneic hematopoietic stem cell transplantation;
• 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;
• Active bacterial or fungal infection identified by clinical diagnosis; a history of active TB or tuberculosis;
• 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;
• Herpesvirus infection (except those who scab for more than 4 weeks); respiratory virus infection (except those who have recovered for more than 4 weeks);
• 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;
• Previous history of drug abuse, clinical or psychological or social factors affecting informed consent or study implementation; a history of mental illness;
• Patients with a history of food, drug or vaccine allergy or other potential immunotherapy allergies as considered by the Investigator.
• Women born during pregnancy or lactation;
• The investigator is not fit for enrollment or may not complete the trial for other reasons.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• First Affiliated Hospital of Zhejiang University Schlool of Medicine — Hangzhou

Identifiers

NCT: NCT06888648 · CISPD-10

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗