A Phase II Study of M7824 in Subjects With Recurrent Respiratory Papillomatosis
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 9
- 试验地点
- 1
- 主要终点
- Proportion of Participants With a Complete Response
研究概览
简要总结
Background:
Programmed cell death protein 1 (PD-L1) is a protein on the surface of cells. It regulates if a cell can be killed by immune system cells. It is thought to be able to affect the immune system response to diseased cells like those infected with a virus. The molecule M7824 interferes with the activity of PD-L1. It could help the immune system kill cells infected with a virus . Since recurrent respiratory papillomatosis is caused by a virus infection, this molecule could help.
Objective:
To see if M7824 works in treating recurrent respiratory papillomatosis.
Eligibility:
Adults ages 18 years or older with recurrent respiratory papillomatosis
Design:
Participants will be screened with:
Medical history
Physical exam
Blood and pregnancy tests
Endoscopy procedure in clinic. A small tube with a camera will look at the inside of the nose, throat, larynx, and upper windpipe.
Some participants will also be screened with a chest scan.
At the start of the study, participants will:
Have a sedated endoscopy procedure where biopsies will be taken.
Have blood tests.
Have apheresis. Blood will be collected by a tube in an arm vein. A machine will remove white blood cells. The rest of the blood will be returned into an arm vein.
Fill out a voice questionnaire.
Participants will get the study molecule into a vein over about 1 hour. They will get it every other week for up to 12 weeks.
Participants will repeat screening and starting procedures throughout the study. They will also review side effects and any medicine they are taking.
When they are done with the study treatment, participants will be evaluated by repeating the study procedures. They may be evaluated periodically until their disease progresses.
详细描述
Background
- Recurrent respiratory papillomatosis (RRP) is a rare papillomatous disease of the aerodigestive tract that is caused by the Human Papilloma Virus (HPV).
- RRP can progress to cause airway compromise, fatal pulmonary lesions, and invasive cancers.
- There is no effective systemic therapy for RRP. Patients typically require repeated interventional procedures for disease control.
- A recently completed phase II clinical trial investigating avelumab in subjects with aggressive RRP demonstrated an acceptable safety profile from Avelumab and a high rate of partial responses.
- RRP is characterized by frequent expression of PD-L1 and transforming growth factor beta (TGF)-beta in the tumor microenvironment.
- This clinical trial will evaluate the activity of M7824, a novel bifunctional fusion protein composed of a fully human Immunoglobulin G1 (IgG1) monoclonal antibody against human PD-L1 (avelumab) fused, via a flexible glycine-serine linker, to the soluble extracellular domain of human TGF- B receptor II (Transforming growth factor, beta receptor II (TGF-BRII), which functions as a TGF-B trap. This drug was selected for its demonstrated activity in a variety of cancers and for its acceptable safety profile.
Objective
- Determine the complete response rate for M7824 in the treatment of patients with RRP.
Eligibility
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 —（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
研究组 & 干预措施
1200 mg intravenous (IV) of M7824
Patients will receive 1200 mg intravenous (IV) of M7824 on day 1 of a 14 day cycle, every other week, for up to 12 weeks total treatment (6 cycles).
干预措施: M7824 (Drug)
结局指标
主要结局
Proportion of Participants With a Complete Response
时间窗: Response was assessed by flexible endoscopy with or without imaging studies before treatment and 6 and 12 weeks after starting treatment.
Complete response for M7824 in the treatment of patients with RRP was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST). Complete Response is defined as no evidence of papillomas on physical exam and/or clinic-based flexible nasopharyngolaryngoscopy and/or tracheoscopy or by exam under anesthesia (sedation or general anesthesia) with endoscopy and biopsies, and absence of disease by imaging if lesions are assessed by imaging.
次要结局
- Number of Participants With a Partial Response(Response was assessed by flexible endoscopy with or without imaging studies before treatment and 6 and 12 weeks after starting treatment.)
- Number of Participants With ≥Grade 3 Adverse Events(Per protocol, adverse events are documented from the first administration of the study therapy, Study Day 1, through 42 days after the study therapy was last administered, up to 24 weeks + 42 days.)
- Number of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0)(Per protocol, adverse events are documented from the first administration of the study therapy, Study Day 1, through 42 days after the study therapy was last administered, up to 24 weeks + 42 days.)
研究者
Scott Norberg, D.O.
Principal Investigator
National Cancer Institute (NCI)