A Sequential Window of Opportunity Trial of Anti-PD-L1/TGF-beta Trap (M7824 ) Alone and in Combination With TriAd Vaccine, and N-803 for Resectable Head and Neck Squamous Cell Carcinoma Not Associated With Human Papillomavirus Infection.
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 21
- 试验地点
- 1
- 主要终点
- Number of Participants Who Experience a Pathologic Complete Response (pCR)
研究概览
简要总结
Background:
Some people who get head and neck cancer will need surgery to treat their cancer. Research suggests that immunotherapy drugs may help fight head and neck cancer if given before surgery. In most cases, there is enough time between cancer diagnosis and surgery to test immunotherapy drugs. In this study, researchers are testing the safety and anti-cancer abilities of 3 drugs given before surgery for head and neck cancer.
Objective:
To learn if giving M7824 alone, or with the TriAd Vaccine (ETBX-011, ETBX-051 & ETBX-061), or with TriAd vaccine plus Anktiva (N-803) can shrink previously untreated head and neck tumors before surgery or stop the tumors from coming back after all treatment.
Eligibility:
People age 18 and older who have a head and neck cancer that has not been treated before, and the tumor must be removed with surgery.
Design:
Participants will be screened in a separate protocol.
Participants will have the following tests:
- medical history and physical exams
- computed tomography or magnetic resonance imaging scans
- tumor, mucosa, and skin biopsies
- electrocardiograms to monitor heart activity
- endoscopies (a tube is inserted through the nose to see the upper airway)
- blood and urine tests.
All participants will get bintrafusp alfa (M7824) through an intravenous infusion. For this, a small plastic tube is put into an arm vein. Some may also get the TriAd vaccine. It is injected under the skin on the arms or legs. Some may also get N-803. It is injected under the skin on the stomach.
Participants will have clinic visits while they are getting treatment and after treatment ends.
After treatment ends, participants will have their scheduled surgery. There will be two follow up visits at the National Institutes of Health (NIH) after your surgery. They will be contacted by phone or email every 2 weeks for 3 months. Then they will be contacted every 3 months for 2 years.
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详细描述
Background:
- Approximately 50% of patients with advanced, non-human papilloma virus (HPV) associated head and neck squamous cell carcinoma (HNSCC) will develop locoregional or distant relapse within two years of completing definitive standard-of-care treatment.
- Two ongoing clinical trials investigating neoadjuvant programmed cell death protein 1 (PD-1) blockade before surgical resection of HNSCC suggest that immunotherapy can both cytoreduce existing disease before surgery and reduce the risk of locoregional or distant disease relapse after surgery.
- Preliminary data from these studies suggest neoadjuvant treatments can be administered without delaying planned surgical intervention.
- Experiments conducted by the Laboratory of Tumor Immunology and Biology (LTIB) demonstrated synergistic activity with tumor-targeted adenoviral vaccine plus bintrafusp alfa (M7824) plus Anktiva (N-803) in humanized mice bearing human carcinomas and in vitro studies.
- M7824 is a bifunctional fusion protein consisting of an anti-programmed death ligand 1(PD-L1) antibody and the extracellular domain of transforming growth factor beta (TGF-beta) receptor type 2, a TGF-beta trap.
- Adenoviral vaccines targeting known shared tumor antigens can generate antigen-specific T cells.
- N-803 is an interleukin 15 (IL-15)/interleukin 15 receptor (IL-15R) alpha super agonist complex that can enhance both natural killer (NK) cell and T cell anti-tumor activity via expansion and activation.
- Activity observed with neoadjuvant anti-PD-1 agents alone provides rationale for testing of M7824 alone and in combination with other immune-oncologic agents that have been shown to work in concert with M7824 in preclinical studies.
- Analysis of pre- and post-treatment tissues from HNSCC patients presents a unique opportunity to interrogate the effects the above treatment(s) on tumor.
- A dose escalation of N-803 in combination with a flat dose of M7824 was conducted at the National Cancer Institute. Thirteen patients have been treated with the combination. No dose limiting toxicities (DLTs) were observed.
Objectives:
-Determine the rate of pathologic complete response (pCR) or clinical-to-pathological downstaging in patients with previously untreated intermediate/high risk, non-HPV associated, squamous cell carcinoma of the head and neck (T1-T4, N0-N3, M0 stage II, III or IV) who receive any of the three proposed treatments: M7824 alone, M7824 plus TriAd vaccine, or M7824 plus TriAd vaccine plus N803 prior to definite surgery.
Eligibility:
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 —（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
Arm A, Cohort 1 Bintrafusp Alfa (M7824) (Days 1, 15)
M7824 (Days 1, 15)
干预措施: M7824 (Drug)
Arm B, Cohort 1 M7824 + TriAd Vaccine (ETBX-011, ETBX-051 & ETBX-061) (Day 1)
M7824 + TriAd vaccine (ETBX-011, ETBX-051 and ETBX-061) (Days 1)
干预措施: M7824 (Drug)
Arm B, Cohort 1 M7824 + TriAd Vaccine (ETBX-011, ETBX-051 & ETBX-061) (Day 1)
M7824 + TriAd vaccine (ETBX-011, ETBX-051 and ETBX-061) (Days 1)
干预措施: TriAd vaccine (Biological)
Arm C, Cohort 1 M7824 + TriAd Vaccine (Day 1) + N-803 (Day 1)
M7824 + TriAd vaccine (Day 1) + N-803 (Day 1)
干预措施: M7824 (Drug)
Arm C, Cohort 1 M7824 + TriAd Vaccine (Day 1) + N-803 (Day 1)
M7824 + TriAd vaccine (Day 1) + N-803 (Day 1)
干预措施: N803 (Drug)
Arm C, Cohort 1 M7824 + TriAd Vaccine (Day 1) + N-803 (Day 1)
M7824 + TriAd vaccine (Day 1) + N-803 (Day 1)
干预措施: TriAd vaccine (Biological)
结局指标
主要结局
Number of Participants Who Experience a Pathologic Complete Response (pCR)
时间窗: Post treatment after on study, approximately one month
Resected tumors were reviewed one month after being on study to determine a pCR, defined as absence of malignant cells in the resected tumor specimen. A pathologist examines tumor specimens to look for malignant cells.
Number of Participants Who Experience Clinical to Pathologic Downstaging Upon Analysis of Resected Tumor After Completing Study Treatments
时间窗: up to 4 months after enrollment
Clinical-to-pathologic downstaging is when the numerical pathological stage is lower than the initial numerical clinical stage (i.e., II to I)
次要结局
- Proportion of Participants With a Complete Response (CR) + Partial Response (PR) Measured by Computed Tomography (CT) Imaging and the Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1(21-28 days from enrollment, up to a maximum of 28 days)
- Number of Participants That Experienced Grade 3 or 4 Immune Related Adverse Events (irAEs)(2 weeks)
- Probability of Being Alive and Recurrence Free(1 and 2 years)
- Percentage of Participants Who Are Alive(Participants were followed to see if they were alive and recurrence free for up to 2 years from study enrollment.)
- Number of Participants With Treatment-related Adverse Events Causing a Delay of 4 Weeks or More Beyond Planned Surgery(4 weeks or more beyond surgery, up to 2 years)
研究者
Hoyoung M. Maeng, M.D.
Principal Investigator
National Cancer Institute (NCI)