Phase II Trial With Safety Run-in of the Anti-Mesothelin Antibody Drug Conjugate Anetumab Ravtansine for Mesothelin Expressing Lung Adenocarcinoma
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 2
- 试验地点
- 1
- 主要终点
- Recommended Phase 2 Dose (RP2D)
研究概览
简要总结
Background:
Anetumab ravtansine is a new drug. It kills cancer cells that carry mesothelin. That is a protein on the surface of tumor cells in many types of tumors, including most lung cancers. Researchers want to find a safe dose for the study drug for lung cancer. They want to see if it can shrink tumors in mesothelin-positive lung cancer.
Objectives:
To test the safety and effectiveness of anetumab ravtansine for lung cancer.
Eligibility:
Adults 18 years and older who have lung cancer that has gotten worse on other therapy
Design:
Participants will be screened with:
Medical history
Physical exam
Tumor tissue sample. This can be from a previous procedure.
Blood and urine tests
Heart tests
Scans. For one scan, a small amount of radioactive substance is injected into the blood.
Eye exam
The study will have 21-day cycles.
On day 1 of each cycle, participants will get the study drug through a tube inserted in a vein.
Participants will repeat a heart test in cycles 1 and 2.
They will have blood tests weekly in cycle 1, twice in all other cycles.
They will have scans every 6 weeks for the first 6 months, every 9 weeks until the end of year 2, then every 12 weeks.
Participants will have samples of tumor tissue taken twice.
About 30 days after stopping the study drug, participants will have a follow-up visit. This will include medical history, physical exam, blood and pregnancy tests, and heart and eye tests.
Some will be called a few times a year to discuss their health and treatment.
详细描述
Background:
- Lung cancer is the leading cause of cancer-related death worldwide, accounting for more than one million deaths every year.
- Non-small-cell lung cancer (NSCLC) constitutes approximately 85% of lung cancers and about 40% of patients with newly diagnosed NSCLC have advanced disease. The median year overall survival for advanced NSCLC is at least 1 year.
- In recent years, identification of oncogenic alterations such as mutations in epidermal growth factor receptor (EGFR) and anaplastic large-cell lymphoma kinase (ALK) translocations and therapies targeting tumor immune escape mechanisms have led to a substantial improvement in the prognosis of patients with advanced lung cancer;
however, such alterations have been detected in less than half of all advanced NSCLC patients in only a small subset of patients respond to immunotherapeutic interventions available today.
- Anetumab ravtansine (BAY 94-9343) is an antibody-drug conjugate targeting mesothelin, a protein normally present on mesothelial cells. A Phase I trial showed the overall acceptable and manageable safety profile. It is being developed for patients with mesothelin expressing cancers; clinical development is furthest along in mesothelioma where it is in a registration phase II clinical trial.
- National Cancer Institute (NCI) researchers have demonstrated that mesothelin messenger ribonucleic acid (mRNA) and protein are present in a substantial number of lung adenocarcinoma cell lines; mesothelin expression has been observed in over 50% of advanced lung adenocarcinomas by immunohistochemical assessment.
Objectives:
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 100 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
研究组 & 干预措施
1/Safety Run-in Arm
Subjects will be dosed with the higher of the 2 possible anetumab ravtansine doses (dose level 1) evaluated on the study
干预措施: Anetumab Ravtansine (Drug)
1/Safety Run-in Arm
Subjects will be dosed with the higher of the 2 possible anetumab ravtansine doses (dose level 1) evaluated on the study
干预措施: Blood test (Device)
2/Phase 2 Arm
Subjects will be dosed with anetumab ravtansine at the recommended phase 2 dose (dose level 1 if no more than 1 dose limiting toxicity (DLT) occurred in the safety run-in arm, or at dose level -1 otherwise)
干预措施: Anetumab Ravtansine (Drug)
2/Phase 2 Arm
Subjects will be dosed with anetumab ravtansine at the recommended phase 2 dose (dose level 1 if no more than 1 dose limiting toxicity (DLT) occurred in the safety run-in arm, or at dose level -1 otherwise)
干预措施: Blood test (Device)
结局指标
主要结局
Recommended Phase 2 Dose (RP2D)
时间窗: 21 days after initiation of study therapy
The highest dose tested at which no more than 1 dose limiting toxicity occurs. A dose limiting toxicity is defined as any treatment emergent adverse event (TEAE) (i.e., absolute neutrophil count \<500/mm\^3 for ≥7 days) occurring during Cycle 1 and regarded to be at least possibly related to anetumab ravtansine.
Proportion of Subjects Who Experienced a Partial or Complete Response
时间窗: 6 weeks
Response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST). A complete response is disappearance of all target lesions. A partial response is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters.
次要结局
- Progression Free Survival(At Disease Progression, approximately 6 weeks.)
- Duration of Response(At Disease Progression, approximately 6 weeks from start of treatment)
- Overall Survival(At Death, an average of 7.5 weeks after start of first cycle for both patients.)
- Number of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0)(Participants on the Safety run-in phase was assessed for approximately two months and 5 days.)
研究者
Raffit Hassan, M.D.
Principal Investigator
National Institutes of Health Clinical Center (CC)