Personalized Tumor Neoantigen mRNA Therapy for Advanced Intrahepatic Cholangiocarcinoma

Официальное название

Clinical Study to Evaluate the Safety and Efficacy of Personalized Tumor Neoantigen mRNA Therapy in Combination With PD-1 Antibody and Chemotherapy for Advanced Intrahepatic Cholangiocarcinoma

Обзор

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.

Вмешательства

• Биопрепарат 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.
• Препарат 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
• Препарат Sintilimab injection
  Sintilimab Injection, 200mg, intravenous infusion

Первичные конечные точки

• Safety and tolerable dose [Срок оценки: 21±3 days after the last dose]

Вторичные конечные точки (5)

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

Критерии участия

Критерии включения

• (1) Subjects who meet all the following inclusion criteria will enter the pre-screening stage of this study and undergo the lesion puncture process:

• 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.

(2) Subjects who meet all the following inclusion criteria will enter the formal screening stage of this study and enter the study medication process:

• Voluntary signing of the informed consent form;
• Age ≥ 18 years and ≤ 75 years, regardless of gender;
• Intrahepatic cholangiocarcinoma confirmed by pathology (histology or cytology);
• Have not received any systemic treatment.
• According to the solid tumor efficacy evaluation criteria (RECIST 1.1), the investigators assessed the patients as having measurable lesions.
• The Eastern Cooperative Oncology Group (ECOG) performance status score was 0 or 1;
• The major organ functions of the heart, liver, and kidney were normal:

• 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 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;
• Able to follow the study protocol and follow-up process.

Критерии исключения

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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• the First Affiliated Hospital, Zhejiang University School of Medicine — Ханчжоу

Идентификаторы

NCT: NCT06956716 · CISLD-14

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗