Phase I/II Open Label Dose Escalation Study of the Safety, Pharmacokinetics, and Preliminary Efficacy of SC16LD6.5 as a Single Agent in Patients With Recurrent Small Cell Lung Cancer
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 82
- 试验地点
- 8
- 主要终点
- Maximum Tolerated Dose (MTD) of Rovalpituzumab Tesirine
研究概览
简要总结
The purpose of this study is to assess the safety and tolerability of rovalpituzumab tesirine (SC16LD6.5) at different dose levels in patients with small cell lung cancer whose cancer has progressed or recurred following standard chemotherapy. Once a safe and tolerable dose is determined, the anti-cancer activity of SC16LD6.5 will be assessed by measuring the extent of tumor shrinkage. SC16LD6.5 is an antibody-drug conjugate (ADC). The antibody (SC16) targets a protein that appears to be expressed on the surface of most small cell lung cancers that have been assessed using an immunohistochemical assay. The drug, D6.5, is a very potent form of chemotherapy, specifically a DNA-damaging agent, that is cell cycle independent. ADC's theoretically provide more precise delivery of chemotherapy to cancer cells, possibly improving effectiveness relative to toxicities.
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
- •Patients who are pregnant or breastfeeding.
- •Active involvement of the Central Nervous System (CNS).
- •Uncontrolled infection or systemic disease.
- •Clinically significant cardiac disease not well controlled with medication (e.g., congestive heart failure, symptomatic coronary artery disease e.g. angina, and cardiac arrhythmias) or myocardial infarction within the last 12 months.
- •Chemotherapy regimens within the last 21 days (or within 6 weeks for prior nitrosourea or mitomycin C). Chemotherapy regimens, biologic, and targeted therapy given continuously or on a weekly basis with limited potential for delayed toxicity within the last 14 days.
- •No concurrent systemic chemotherapy or anticancer biologic therapy is allowed. Note: Patients on hormonal treatment for breast cancer or prostate cancer may continue on treatment and enter into study.
- •Known hypersensitivity to any components of SC16LD6.5 study drug product.
- •Patients with known human immunodeficiency virus (HIV) or Hepatitis B or C (active, previously treated or both), a history of solid organ or bone marrow transplantation would generally be considered to have met exclusion criteria, however exceptions may be considered on a case-by-case basis by the medical monitor.
- •Psychiatric disorder or social or geographic situation that would preclude study participation.
- •QT interval measurement corrected by Fridericia's formula (QTcF) interval of >450 msec (males) or >470 msec (females)
研究组 & 干预措施
Rovalpituzumab tesirine
Rovalpituzumab tesirine will be administered as a single agent, at increasing dose levels as permitted based on real-time assessment of safety and tolerability, intravenously over 30 minutes. Doses will be repeated on Day 1 of each 21-day or 42-day cycle until either unacceptable toxicity or evidence of disease progression occurs.
干预措施: Rovalpituzumab tesirine (SC16LD6.5) (Drug)
结局指标
主要结局
Maximum Tolerated Dose (MTD) of Rovalpituzumab Tesirine
时间窗: The DLT period was defined as either 21 or 42 days following the first dose of Rovalpituzumab tesirine during dose escalation (Phase 1a), depending on Cycle length.
MTD was determined by testing increasing doses from 0.05 mg/kg up to 0.8 mg/kg on Day 1 of every 21-day or 42-day cycle, Phase 1a cohorts 1 to 8. MTD will be defined as the dose level immediately below the dose level at which ≥ 2 of the first 3 subjects per cohort (or ≥ 2 of 6 subjects) during the first cycle experience a study drug related dose limiting toxicity (DLT).
次要结局
- Objective Response Rate (ORR)(From first dose of rovalpituzumab tesirine to last event, up through study completion (on average approximately 4 months).)
- Clinical Benefit Rate (CBR)(From first dose of Rovalpituzumab tesirine to last event timepoint, up through study completion (on avergae approximately 4 months).)
- Duration of Response (DOR)(From first dose of Rovalpituzumab tesirine to last event timepoint, up through study completion (on average approximately 4 months, but up to 6.51 months).)
- Overall Survival(From first dose of Rovalpituzumab tesirine to last event, up through study completion (on average approximately 5-7 months, but up to 14.6 months).)
- Progression-free Survival (PFS)(From first dose of rovalpituzumab tesirine to last event timepoint, up through study completion (approximately 4 months on average, but up to 14.46 months).)
- Maximum Serum Concentration (Cmax) of Rovalpituzumab Tesirine Antibody Drug Conjugate (ADC)(From Day 1 of first dose to End of Dose Cycle)
- Area Under the Serum Concentration-time Curve (AUC) of Rovalpituzumab Tesirine ADC(From Day 1 of first dose to End of Dose Cycle)