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.
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Occurence and frequence of AE and SAE
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •(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.
排除标准
- •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.
研究组 & 干预措施
Arm A
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.
干预措施: individualized anti-tumor new antigen iNeo-Vac-R01 injection (Biological)
Arm A
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.
干预措施: mFOLFIRINOX Treatment Regimen (Drug)
Arm A
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.
干预措施: Sintilimab injection (Drug)
结局指标
主要结局
Occurence and frequence of AE and SAE
时间窗: Up to 2 years
Occurence and frequence of Adverse Event (AE) and Serious Adverse Event (SAE) (NCI CTCAE 5.0)
次要结局
- 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)
- Overall Survival Rate (1-Y-OS%,2-Y-OS%,3-Y-OS%)(Up to 3 years)
研究者
TingBo Liang
The chairman of the First Affiliated Hospital of Zhejiang University School of Medicine
First Affiliated Hospital of Zhejiang University