Personalized Tumor Neoantigen mRNA Therapy for Advanced Intrahepatic Cholangiocarcinoma

NCT06956716 | Recruiting Phase 1

• 1 other identifier: CISLD-14
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

The main purpose of this study is to evaluate the feasibility and safety of personalized tumor neoantigen mRNA therapy iNeo-Vac-R01 combined with PD-1 monoclonal antibody and standard chemotherapy regimen for the treatment of patients with advanced intrahepatic cholangiocarcinoma.

Conditions

Advanced Intrahepatic Cholangiocarcinoma

Outcome Measures

Primary Outcomes (1)

• Safety and tolerable dose

  According to the Commonly Used Adverse Events Criteria (CTCAE Version 5.0), the number of subjects with adverse events and/or dose-limiting toxicity was counted as an indicator of the safety and tolerable dose of iNeo-Vac-R01 injection. The evaluation period was the dosing observation period and the safety follow-up period.

  21±3 days after the last dose

Secondary Outcomes (5)

• 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

• Overall Survival Rate (1-Y-OS%,2-Y-OS%,3-Y-OS%)

  Up to 3 years

Study Arms (1)

A

EXPERIMENTAL

Biological: individualized anti-tumor new antigen iNeo-Vac-R01 injection; Drug: Gemcitabine + cisplatin (GP); 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.

A

Gemcitabine + cisplatin (GP) DRUG

As standard chemotherapy (D1, D8 gemcitabine 1000mg/m², intravenous drip for 30 minutes, cisplatin 25mg/m², intravenous drip), once every 3 weeks

A

Sintilimab injection DRUG

Sintilimab Injection, 200mg, intravenous infusion

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:

• Voluntarily sign the informed consent form;
• Aged ≥18 years and ≤75 years, regardless of gender;
• Imaging assessment of unresectable advanced intrahepatic cholangiocarcinoma;
• Have not received systemic or local treatment.
• According to the solid tumor efficacy evaluation criteria (RECIST 1.1), the investigators assess the lesions as measurable.
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1;
• Adequate fresh tumor tissue samples can be obtained for exome and transcriptome sequencing analysis;
• Normal function of the main organs of the heart, liver and kidney:
• QTc (corrected QT interval) in the electrocardiogram: ≤450 milliseconds for men, or ≤470 milliseconds for women;
• Coagulation function: international normalized ratio (INR) ≤1.5×ULN; activated partial thromboplastin time (APTT) ≤1.5 times ULN;
• Hematological indicators: white blood cells ≥3.5×109/L; absolute neutrophil count (ANC) ≥1.5×109/L; hemoglobin (HGB) ≥10 g/dL; platelet count (PLT) ≥80×109/L;
• Biochemical indicators: serum total bilirubin (TBIL) ≤ 1.5 times the upper limit of normal (ULN); alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 times ULN (ALT or AST ≤ 5 times ULN is allowed for patients with liver metastasis and liver cancer); serum creatinine and urea nitrogen ≤ 1.5 times ULN;
• Male and female patients of childbearing age with fertility agree to take effective contraceptive measures from the signing of the informed consent form to 6 months after the last dose of the trial drug; women of childbearing age include premenopausal women and women within 2 years after menopause;
• Able to follow the study protocol and follow-up procedures.
• Voluntary signing of the informed consent form;

You may not qualify if:

• If the subject meets any of the following criteria, he/she will be excluded from this study:
• Those who suffer from other malignant tumors at the same time, but have been cured of basal cell carcinoma, thyroid cancer, cervical atypical hyperplasia, etc., have been in a disease-free state for more than 5 years or are considered by the researchers to be less likely to relapse;
• Those who have received a history of bone marrow transplantation, allogeneic organ transplantation, or allogeneic hematopoietic stem cell transplantation;
• Those who are accompanied by immunosuppressants, that is, those who need to take immunosuppressants regularly 4 weeks before the screening period and during the clinical study, including but not limited to the following situations: those with severe asthma, autoimmune diseases or immunodeficiency, those who are treated with immunosuppressive drugs, and those with a known history of primary immunodeficiency; but type 1 diabetes, autoimmune-related hypothyroidism requiring hormone treatment, and vitiligo and psoriasis that do not require systemic treatment are excluded;
• Active bacterial or fungal infection confirmed by clinical diagnosis; active tuberculosis or history of tuberculosis;
• Positive test results for human immunodeficiency virus (HIV) antibody, positive test results for Treponema pallidum (TP), active hepatitis C (positive hepatitis C virus (HCV) antibody and positive HCV RNA), active hepatitis B;
• Herpes virus infection (except for those with scabs for more than 4 weeks); respiratory virus infection (except for those who have recovered for more than 4 weeks);
• History of drug abuse, clinical, psychological or social factors that affect informed consent or research implementation; history of mental illness;
• History of food, drug or vaccine allergy, or other potential immunotherapy allergy considered by the investigator.
• Pregnant or lactating women;

Sponsors & Collaborators

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

Study Sites (1)

the First Affiliated Hospital, Zhejiang University School of Medicine

Hangzhou, Zhejiang, 310003, China

RECRUITING

MeSH Terms

Interventions

Gemcitabine; Cisplatin; sintilimab

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Central Study Contacts

Tingbo Liang

CONTACT

+8619941463683; liangtingbo@zju.edu.cn

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: April 9, 2025
• First Posted: May 4, 2025
• Study Start: April 9, 2025
• Primary Completion (Estimated): April 1, 2027
• Study Completion (Estimated): April 1, 2028
• Last Updated: May 4, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)