Personalized Neoantigen Derived Dendritic Cell-Based Immunotherapy as Cancer Treatment
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 12
- 试验地点
- 3
- 主要终点
- Number of subjects experienced limiting toxicities in the first 6 weeks.
研究概览
简要总结
Tumor lysate or carcinoembryonic antigen (CEA) derived DCs-based therapy is safe and can elicites remarkable T-cell responses but mostly did not really transfer into significant clinical benefit. One possible reason is the lack of effective antigen and the immunosuppressive microenvironment. Now we are exploring another new strategy, prediction of neoantigen for priming DCs as cell-based therapy with or without booster of anti-VEGF/anti-PD-1.
详细描述
The human immune system can recognize and destroy cancer cells but cancer cells are capable of escaping from immune system by different ways, including the PD-1/PDL-1 axis and the VEGF signaling pathway. The PD-1/PD-L1 axis represents an adaptive immune resistance mechanism exerted by tumor cells. Previous study also revealed VEGF-A could induce tumor-associated macrophages, Treg cells, and myeloid-derived suppressor cells, creating an immunosuppressive microenvironment that prevent the maturation of dendritic cells (DCs) and inhibit the activation of NK cells and T cells. Our research group already completed some early phase clinical trials of DCs-based therapy, which illustrated tumor lysate or carcinoembryonic antigen (CEA) derived DCs-based therapy is feasible and safe in patients with advanced colorectal cancer and lung cancer, respectively. However, although DCs-based therapy elicited remarkable T-cell responses but mostly did not really transfer into significant clinical benefit in previous study. One possible reason is the lack of effective antigen and the immunosuppressive microenvironment. Now we are exploring another new strategy, prediction of neoantigen for priming DCs as cell-based therapy with or without booster of anti-VEGF/anti-PD-1.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 20 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •≥20 years of age
- •Provide written informed consent
- •Histologically confirmed stage IV pancreatic cancer, liver cancer, biliary tract cancer and colorectal cancer (excluding sarcoma and neuroendocrine tumor) that refractory or intolerance to standard therapies for their condition (there is no effective treatment by investigator judgement)
- •Completed tumor and germline DNA and RNA sequencing and the neoantigen prediction
- •Patients with chronic hepatitis B is eligible if receiving anti-hepatitis B agents and the HBV DNA level < 2000 IU/ml prior to the preparation phase. Patients with chronic hepatitis C are eligible if HCV RNA is undetectable (<15 IU/ml) prior to the preparation phase
- •Adequate organ function
- •Absolute neutrophil count >1000/mcL
- •Hemoglobin > 8.0 g/dl
- •Platelet > 50000/mcL
- •PT/aPTT < 1.5 x upper limit of normal (ULN)
- •AST/ALT < 3 x ULN
- •Bil(T) < 1.5 x ULN
- •BUN/Cr < 1.5 x ULN
- •Adequate immune system as defined by
- •IgG > 614 mg/dl
- •IgM > 53mg/dl
- •Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2
- •Life expectancy at least>12weeks
- •At least one measurable target lesion as defined by RECIST 1.1
排除标准
- •Sarcoma、neuroendocrine tumor
- •Last anticancer therapy administered within 2 weeks and any AEs should be ≤ grade 2 prior to leukapheresis
- •Patients who cannot tolerate leukapheresis and follow-up blood sampling of 50ml at day 43, day 85 and end-of- treatment.
- •Any known active infection as judged by the investigator
- •Any known chronic active infection of HIV, HTLV-1 or HTLV-2
- •Requirement of systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days prior to the screen phase. Inhaled or topical steroids and adrenal replacement doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.
- •Other immunocompromising condition that in the opinion of the treating physician renders the patient a poor candidate for this trial
- •Pregnant women, nursing women, men or women of childbearing potential who are unwilling to employ adequate contraception (condoms, diaphragm, birth control pills, injections, intrauterine device (IUD), abstinence, etc.)
- •Patients with history of penicillin allergy
- •Other medical problems or conditions that, in the opinion of the investigator, would make participation in the study hazardous for the patient
研究组 & 干预措施
Arm 1: DCs monotherapy
DCs injection on day 1, 8, 15, 29, 85, 141, 197, 253 and 309.
干预措施: Dendritic Cell Vaccine (Biological)
Arm 2: DCs with booster of anti-VEGF/anti-PD-1.
DCs injection on day 1, 8, 15, 29, 85, 141, 197, 253 and 309 plus lenvatinib 10mg QD on day 43-77 and nivolumab 3mg/kg on day 43, 57 and 71.
干预措施: Dendritic Cell Vaccine (Biological)
Arm 2: DCs with booster of anti-VEGF/anti-PD-1.
DCs injection on day 1, 8, 15, 29, 85, 141, 197, 253 and 309 plus lenvatinib 10mg QD on day 43-77 and nivolumab 3mg/kg on day 43, 57 and 71.
干预措施: Lenvatinib (Drug)
Arm 2: DCs with booster of anti-VEGF/anti-PD-1.
DCs injection on day 1, 8, 15, 29, 85, 141, 197, 253 and 309 plus lenvatinib 10mg QD on day 43-77 and nivolumab 3mg/kg on day 43, 57 and 71.
干预措施: Nivolumab (Drug)
结局指标
主要结局
Number of subjects experienced limiting toxicities in the first 6 weeks.
时间窗: 6 weeks
The following toxicities that happened during first 6 weeks are considered LTs. Toxicities are graded using Common Terminology Criteria for Adverse Events (CTCAE) version 5.0: * \>=Grade 3 non-hematological toxicity * \>=Grade 4 hematological toxicity * Any death not clearly due to the underlying disease or extraneous causes. * Any case meeting Hy's law * Recurrent grade 2 pneumonitis
次要结局
- Number of participants who did not progressed or survived at 1 year(1 year)
- Number of subjects experienced any ≥ grade 3 toxicities.(1 year)
- Percentage of patients who had a clinical response(1 year)