Personalized Tumor Neoantigen MRNA Therapy for Advanced Pancreatic Cancer.

NCT06888648 | Not Yet Recruiting Phase 1

• 1 other identifier: CISPD-10
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

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.

Conditions

Pancreatic Cancer Metastatic; Pancreatic Cancer Non-resectable

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (6)

• Objective reponse rate (ORR)

  Up to 2 years

• Disease control rate (DCR)

  Up to 2 years

• Progression-free survival （PFS）

  Up to 2 years

• Overall survival (OS)

  Up to 2 years

• Progression-free survival Rate（1-Y-PFS%, 2-Y-PFS%,3-Y-PFS%）

  Up to 3 years

Study Arms (1)

Arm A

EXPERIMENTAL

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.

Biological: individualized anti-tumor new antigen iNeo-Vac-R01 injection; Drug: mFOLFIRINOX Treatment Regimen; Drug: Sintilimab injection

Interventions

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

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.

Arm A

mFOLFIRINOX Treatment Regimen DRUG

continuous intravenous infusion of fluorouracil 2400mg / m², for 46 hours, leucovorin 400mg / m², irinotecan 135mg / m², and oxaliplatin 68mg / m², every 2 weeks

Arm A

Sintilimab injection DRUG

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

Arm A

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• (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);

You may not qualify if:

• 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.

Sponsors & Collaborators

• Zhejiang University: lead
• Hangzhou Neoantigen Therapeutics Co., Ltd.: collaborator

Study Sites (1)

First Affiliated Hospital of Zhejiang University Schlool of Medicine

Hangzhou, Zhejiang, 31000, China

Location

MeSH Terms

Interventions

sintilimab

Central Study Contacts

Tingbo Liang, MD., PhD.

CONTACT

+8619941463683; liangtingbo@zju.edu.cn

Yiwen Chen, MD.

CONTACT

+8615088682641; yiwenchen0705@126.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: The chairman of the First Affiliated Hospital of Zhejiang University School of Medicine

Study Record Dates

• First Submitted: March 15, 2025
• First Posted: March 21, 2025
• Study Start: April 1, 2025
• Primary Completion (Estimated): April 1, 2027
• Study Completion (Estimated): April 1, 2028
• Last Updated: March 21, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)