Personalized Tumor Neoantigen mRNA Therapy for Advanced Intrahepatic Cholangiocarcinoma

NCT ID: NCT06956716

Last Updated: 2025-05-04

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-04-09
• Study Completion Date: 2028-04-01

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

A

Group Type: EXPERIMENTAL

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

Intervention Type: 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.

Gemcitabine + cisplatin (GP)

Intervention Type: DRUG

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

Sintilimab injection

Intervention Type: DRUG

Sintilimab Injection, 200mg, intravenous infusion

Interventions

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.

Intervention Type: BIOLOGICAL

Gemcitabine + cisplatin (GP)

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

Intervention Type: DRUG

Sintilimab injection

Sintilimab Injection, 200mg, intravenous infusion

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Voluntarily sign the informed consent form;

2. Aged ≥18 years and ≤75 years, regardless of gender;

3. Imaging assessment of unresectable advanced intrahepatic cholangiocarcinoma;

4. Have not received systemic or local treatment.

5. According to the solid tumor efficacy evaluation criteria (RECIST 1.1), the investigators assess the lesions as measurable.

6. Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1;

7. Adequate fresh tumor tissue samples can be obtained for exome and transcriptome sequencing analysis;

8. Normal function of the main organs of the heart, liver and kidney:

1. QTc (corrected QT interval) in the electrocardiogram: ≤450 milliseconds for men, or ≤470 milliseconds for women;

2. Coagulation function: international normalized ratio (INR) ≤1.5×ULN; activated partial thromboplastin time (APTT) ≤1.5 times ULN;

3. 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;

4. 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;

9. 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;

10. Able to follow the study protocol and follow-up procedures.

1. Voluntary signing of the informed consent form;

2. Age ≥ 18 years and ≤ 75 years, regardless of gender;

3. Intrahepatic cholangiocarcinoma confirmed by pathology (histology or cytology);

4. Have not received any systemic treatment.

5. According to the solid tumor efficacy evaluation criteria (RECIST 1.1), the investigators assessed the patients as having measurable lesions.

6. The Eastern Cooperative Oncology Group (ECOG) performance status score was 0 or 1;

7. The major organ functions of the heart, liver, and kidney were normal:

1. QTc (corrected QT interval) in the electrocardiogram: ≤450 milliseconds for men or ≤470 milliseconds for women;

2. Coagulation function: international normalized ratio (INR) ≤1.5×ULN; activated partial thromboplastin time (APTT) ≤1.5 times ULN;

3. 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;

4. 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;

8. Male patients with fertility and female patients of childbearing age agree to take effective contraceptive measures from the signing of the informed consent form to 6 months after the last administration of the trial drug; women of childbearing age include premenopausal women and women within 2 years after menopause;

9. Able to follow the study protocol and follow-up process.

Exclusion Criteria

• If the subject meets any of the following criteria, he/she will be excluded from this study:

1. 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;

2. Those who have received a history of bone marrow transplantation, allogeneic organ transplantation, or allogeneic hematopoietic stem cell transplantation;

3. 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;

4. Active bacterial or fungal infection confirmed by clinical diagnosis; active tuberculosis or history of tuberculosis;

5. 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;

6. 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);

7. 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 that the investigator considers unsuitable for inclusion;

8. History of drug abuse, clinical, psychological or social factors that affect informed consent or research implementation; history of mental illness;

9. History of food, drug or vaccine allergy, or other potential immunotherapy allergy considered by the investigator.

10. Pregnant or lactating women;

11. Those who the investigator considers unsuitable for inclusion or may not be able to complete this trial for other reasons.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hangzhou Neoantigen Therapeutics Co., Ltd.

INDUSTRY

Sponsor Role: collaborator

Zhejiang University

OTHER

Sponsor Role: lead

Responsible Party

TingBo Liang

The chairman of the First Affiliated Hospital of Zhejiang University School of Medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

the First Affiliated Hospital, Zhejiang University School of Medicine

Hangzhou, Zhejiang, China

Site Status: RECRUITING

Countries

China

Central Contacts

Tingbo Liang

Role: CONTACT

liangtingbo@zju.edu.cn

+8619941463683

Facility Contacts

Yiwen Chen

Role: primary

yiwenchen0705@126.com

+8619941463683

Other Identifiers

CISLD-14

Identifier Type: -

Identifier Source: org_study_id