Phase II Trial of M7824 in Subjects With HPV Associated Malignancies
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 57
- 试验地点
- 1
- 主要终点
- Percentage of Participants That Achieved an Objective Confirmed Complete or Partial Overall Tumor Response
研究概览
简要总结
Background:
In the United States, each year there are more than 30,000 cases of human papillomavirus (HPV) associated cancers. Some of these cancers are often incurable and are not improved by standard therapies. Researchers want to see if a new drug M7824, which targets and blocks a pathway that prevents the immune system from effectively fighting the cancer can shrink tumors in people with some HPV cancers.
Objectives:
To see if the drug M7824 causes tumors to shrink.
Eligibility:
Adults age 18 and older who have a cancer associated with HPV infection.
Design:
Participants will be screened with medical history and physical exam. They will review their symptoms and how they perform normal activities. They will have body scans. They will give blood and urine samples. They will have a sample of their tumor tissue taken if one is not available.
Participants will have an electrocardiogram to evaluate their heart. Then they will get the study drug through a thin tube in an arm vein.
Participants will get the drug every 2 weeks for 26 times (1 year). This is 1 course.
After the course, participants will be monitored but will not take the study drug. If their condition gets worse, they will start another course with the drug. This process can be repeated as many times as needed.
Treatment will stop if the participant has bad side effects or the drug stops working.
Throughout the study, participants will repeat some or all the screening tests.
After participants stop taking the drug, they will have a follow-up visit and repeat some screening tests. They will get periodic follow-up phone calls.
详细描述
Background:
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Metastatic or refractory/recurrent human papillomavirus (HPV) associated malignancies (cervical, anal, oropharyngeal cancers etc.) are often incurable and poorly palliated by standard therapies.
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Transforming growth factor receptor type 1 (TGF R1) pathway signaling and overexpression are significantly associated with HPV+ cancers.
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Programmed cell death protein 1 (PD-1) inhibitors have produced a 12-20% response rate for these diseases
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M7824 is a novel bifunctional fusion protein composed of monoclonal antibodies against human programmed death-ligand 1 (PD- L1) and soluble extracellular domain of human TGF- receptor II (TGF- RII), which functions as a TGF- "trap."
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Early data from a small cohort of patients with HPV associated malignancies in a phase I trial of M7824 has shown promising activity (NCT02517398). As of May 30, 2017, 4 of 9 patients (44%) with HPV associated malignancies have had preliminary evidence of clinical benefit including:
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Patient with metastatic cervical cancer with a 25% reduction in her disease at 3 months
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Patient with metastatic P16 positive (P16+) head and neck cancer with an unconfirmed partial response (PR) at 6 weeks
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Patient with metastatic anal cancer with a durable PR ongoing 9 months after starting treatment
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Patient with metastatic cervical cancer with a durable complete response (CR) ongoing 15 months after starting treatment.
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Notably, the P16+ head and neck cancer patient with unconfirmed PR, anal cancer patient with durable PR and cervical cancer patient with durable CR all have HPV+ disease.
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Immune related adverse events with M7824 in the phase I trial to date have been on par with other PD-1/PD-L1 inhibitors, suggesting a manageable safety profile.
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EMD Serono has an ongoing expansion cohort evaluating M7824 in patients with head and neck squamous cell carcinoma (HNSCC) as well as in cervical cancer excluding neuroendocrine cervical cancer.
Objective:
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
1/Arm 1-M7824 1,200 mg intravenous (IV) once every 2 weeks
M7824 at a flat dose of 1,200 mg intravenous (IV) once every 2 weeks
干预措施: M7824 (Drug)
结局指标
主要结局
Percentage of Participants That Achieved an Objective Confirmed Complete or Partial Overall Tumor Response
时间窗: Every six weeks for up to one year
The percentage of participants that achieved an objective confirmed complete or partial overall tumor response was measured using the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Complete response is disappearance of all target lesions. Partial response is at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
次要结局
- Progression-free Survival Time (PFS)(Time from the date of first treatment to the date of disease progression or death, up to 12 months)
- Percentage of Participants With Disease Control Who Achieved a Complete Response, Partial Response and Stable Disease Defined by the Response Evaluation Criteria in Solid Tumors (RECIST)Version 1.1 Lasting at Least 6 Months(6 months)
- Overall Survival (OS)(Time from the date of first treatment to the date of death, up to 3 years.)
- Number of Participants With Serious Grade ≥3 Adverse Events Considered Related to Study Treatment of M7824(28 days after treatment)
- Number of Checkpoint Inhibitor Naive Participants With Response Based on Adequate Similarity (Defined as P-value > 0.2 With Fisher's Exact Test) of Results in Cohorts 1 and 2(median of 2 years)
- Percentage of Participants That Were Hospitalized Because of Adverse Events Attributed to Disease Progression(Up to 30 days from last treatment)
- Duration of Response (Complete Response or Partial Response)(Time from complete response or partial response (whichever is first recorded) until the first date that recurrent or progressive disease (PD) is objectively documented, up to 12 months)
研究者
Julius Strauss, M.D.
Principal Investigator
National Cancer Institute (NCI)