A Phase I/II Trial to Evaluate the Safety and Immunogenicity of a Messenger RNA (mRNA)-Based, Personalized Cancer Vaccine Against Neoantigens Expressed by the Autologous Cancer
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 5
- 试验地点
- 2
- 主要终点
- Number of Participants Who Had a Clinical Response (Complete Response + Partial Response) to Treatment (Objective Tumor Regression)
研究概览
简要总结
Background:
Exome sequencing can identify certain gene mutations in a person's tumor. This can then be used to create cancer treatments. In this study, researchers will make a treatment called a messenger ribonucleic acid (mRNA) vaccine. The vaccine might cause certain tumors to shrink.
Objective:
To see if the mRNA vaccine is safe and can cause metastatic melanoma or epithelial tumors to shrink.
Eligibility:
People 18-70 years old with metastatic melanoma or epithelial cancer
Design:
Participants will be screened under protocol 99-C-0128.
Participants will provide samples under protocol 03-C-0277:
Participants will provide a piece of their tumor from a previous surgery or biopsy.
Participants will have leukapheresis: Blood is removed through a needle in one arm and circulated through a machine that takes out the white blood cells. The blood is then returned through a needle in the other arm.
Participants will have many tests:
Scans and x-rays
Heart and lung function tests
Blood and urine tests
Participants will receive the mRNA vaccine every 2 weeks for up to 8 weeks. They will get the vaccine as an injection into the upper arm or thigh. They may receive a second course of vaccines if the study doctor determines it is needed.
Participants will have follow-up visits approximately 2 weeks after their final vaccine, then 1 month later, then every 1-2 months for the first year, and then once a year for up to 5 years. Each visit may take up to 2 days and include:
Physical exam
Blood tests
Scans
Leukapheresis at the first visit
详细描述
Background:
- Therapeutic vaccination against cancer has proven very challenging with little clinical benefit.
- Vaccines against non-viral tumors have mainly targeted differentiation antigens, cancer testis antigens, and overexpressed antigens. However, negative selection in the thymus against these normal non-mutated antigens severely limits the ability to generate high avidity anti-cancer T-cells. Such depletion can impair their antitumor activity and limit tumor elimination.
- The National Cancer Institute Surgery Branch (NCI-SB) has developed a pipeline for the identification of immunogenic T-cell epitopes derived from neoantigens.
- In recent studies, we identified the neoantigens recognized by tumor-infiltrating lymphocytes (TIL) that mediated regression in patients with metastatic melanoma. Using whole exome sequencing of a resected metastatic nodule followed by high throughput immunologic screening, we were able to demonstrate that tumor regressions were associated with the recognition by the administered TIL of unique somatic mutations that occurred in the cancer.
- We also found that TIL from 29 of 32 patients with a wide variety of metastatic gastrointestinal cancers contained lymphocytes that recognized unique mutations presented in that patient's cancer.
- We, therefore, aim to use this pipeline to identify immunogenic neoantigens and to predict for neoantigens binding the patient human leukocyte antigen (HLA) molecules from melanoma or epithelial cancer patients and to use these epitopes for a personalized therapeutic messenger ribonucleic acid (mRNA) vaccine.
Objectives
Primary objectives:
- Determine the clinical response rate in patients with metastatic melanoma, gastrointestinal or genitourinary cancers who receive NCI-4650
- Determine the safety of NCI-4650 in patients with metastatic melanoma, gastrointestinal or genitourinary cancers
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
结局指标
主要结局
Number of Participants Who Had a Clinical Response (Complete Response + Partial Response) to Treatment (Objective Tumor Regression)
时间窗: up to 12 months
Clinical response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Complete Response (CR) is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm. Partial Response (PR) is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters. Stable Disease (SD) is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum of diameters while on study. Progressive Disease (PD) is at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered progression.
Number of Non-Serious Adverse Events Probably Related to Treatment
时间窗: During treatment and up to 30 days after the first follow- up evaluation (at the second follow-up evaluation)
Here is the number of non-serious adverse events probably related to treatment assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0).
次要结局
- Number of Participants With an Increase in the Quantity and Quality of Circulating Antigen-specific T Cells(Approximately 2 weeks after last vaccine)
研究者
Steven Rosenberg, M.D.
Principal Investigator
National Cancer Institute (NCI)