NCT02674568已完成2 期
An Open-label, Single-Arm, Phase 2 Study Evaluating the Efficacy, Safety and Pharmacokinetics of Rovalpituzumab Tesirine (SC16LD6.5) for Third-line and Later Treatment of Subjects With Relapsed or Refractory Delta-Like Protein 3-Expressing Small Cell Lung Cancer (TRINITY)
AbbVie0 个研究点目标入组 342 人开始时间: 2016年1月25日最近更新:
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 342
- 主要终点
- Overall Survival
研究概览
简要总结
The purpose of this study is to determine the efficacy of rovalpituzumab tesirine as a third-line and later treatment for participants with relapsed or refractory delta-like protein 3 (DLL3) expressing small cell lung cancer (SCLC).
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）
- 接受健康志愿者
- 否
入选标准
- •Adult aged 18 years or older
- •Histologically confirmed SCLC with documented disease progression after at least 2 prior systemic regimens, including at least one platinum-based regimen
- •DLL3-expressing SCLC based on central immunohistochemistry (IHC) assessment of banked or otherwise representative tumor tissue. Positive is defined as staining in ≥ 1% of tumor cells
- •Measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- •Minimum life expectancy of at least 12 weeks
- •Subjects with a history of central nervous system (CNS) metastases must have documentation of stable or improved status based on brain imaging for at least 2 weeks after completion of definitive treatment and within 2 weeks prior to first dose of study drug, off or on a stable dose of corticosteroids
- •Recovery to Grade 1 of any clinically significant toxicity (excluding alopecia) prior to initiation of study drug administration
- •Adequate hematologic and organ function as confirmed by laboratory values
- •Last dose of any prior therapy administered by the following time intervals before the first dose of study drug:
- •Chemotherapy, small molecule inhibitors, radiation, and/or other investigational anticancer agents (excluding investigational monoclonal antibodies): 2 weeks
- •Immune-checkpoint inhibitors (i.e., anti-PD-1, anti-PD-L1, or anti-CTLA-4): 4 weeks
- •Other monoclonal antibodies, antibody-drug conjugates, radioimmunoconjugates, or T-cell or other cell-based therapies: 4 weeks (2 weeks with documented disease progression)
- •Females of childbearing potential must have a negative beta human chorionic gonadotropin (β-hCG) pregnancy test result within 7 days prior to the first dose of study drug. Females of non-childbearing potential are those who are postmenopausal greater than 1 year or who have had a bilateral tubal ligation or hysterectomy.
排除标准
- •Any significant medical condition, including any suggested by screening laboratory findings that, in the opinion of the investigator or sponsor, may place the subject at undue risk from the study, including but not necessarily limited to uncontrolled hypertension and/or diabetes, clinically significant pulmonary disease (e.g., chronic obstructive pulmonary disease requiring hospitalization within 6 months) or neurological disorder (e.g., seizure disorder active within 6 months)
- •Documented history of a cerebral vascular event (stroke or transient ischemic attack), unstable angina, myocardial infarction, or cardiac symptoms consistent with New York Heart Association (NYHA) Class III-IV within 6 months prior to their first dose of study drug
- •Recent or ongoing serious infection, including:
- •Any active grade 3 or higher (per National Cancer Institute's Common Terminology Criteria for Adverse Events [NCI CTCAE] version 4.03) viral, bacterial, or fungal infection within 2 weeks of the first dose of the study drug. Routine antimicrobial prophylaxis is permitted.
- •Known seropositivity for or active infection by human immunodeficiency virus (HIV)
- •Active Hepatitis B (by surface antigen expression or polymerase chain reaction) or C (by polymerase chain reaction) infection or on hepatitis-related antiviral therapy within 6 months of first dose of study drug.
- •Women who are breastfeeding
- •Systemic therapy with corticosteroids at >20 mg/day prednisone or equivalent within 1 week prior to the first dose of study drug
- •History of another invasive malignancy that has not been in remission for at least 3 years. Exceptions to the 3 year limit include nonmelanoma skin cancer, curatively treated localized prostate cancer, and cervical cancer in situ on biopsy or squamous intraepithelial lesion on pap smear
- •Prior exposure to a pyrrolobenzodiazepine (PBD)-based drug, or known hypersensitivity to rovalpituzumab tesirine or excipient contained in the drug formulation, unless undergoing retreatment with rovalpituzumab tesirine in the context of this protocol
研究组 & 干预措施
Rovalpituzumab Tesirine
Experimental
0.3 mg/kg rovalpituzumab tesirine administered intravenously on Day 1 of each 42-day cycle (every 6 weeks; Q6W) for 2 cycles. An additional 2 cycles of rovalpituzumab tesirine (retreatment) was permitted for eligible participants.
干预措施: Rovalpituzumab tesirine (Drug)
结局指标
主要结局
Overall Survival
时间窗: up to 122.4 weeks; mean (SD) duration of follow-up was 29.0 (23.77) weeks
Overall survival is defined as the time from the first dose date to death for any reason. Participants who were alive at the clinical data cut-off were censored at the last known alive date. Based on Kaplan-Meier estimates.
Objective Response Rate
时间窗: up to 122.4 weeks; mean (SD) duration of follow-up was 29.0 (23.77) weeks
Objective response is defined as a participant with the best overall response of complete response (CR) or partial response (PR), per Response Evaluation Criteria in Solid Tumors (RECIST) v 1.1, prior to receiving any subsequent anticancer therapy and retreatment, and is confirmed by a consecutive response assessment at least 4 weeks (28 days) from the initial determination of CR/PR. Analyzed based on response assessments from both the Independent Review Committee (IRC) and investigators. CR: disappearance of all target lesions.Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
次要结局
- Duration of Objective Response(up to 122.4 weeks; mean (SD) duration of follow-up was 29.0 (23.77) weeks)
- Duration of Clinical Benefit(up to 122.4 weeks; mean (SD) duration of follow-up was 29.0 (23.77) weeks)
- Clinical Benefit Rate(up to 122.4 weeks; mean (SD) duration of follow-up was 29.0 (23.77) weeks)
- Overall Response Rate(up to 122.4 weeks; mean (SD) duration of follow-up was 29.0 (23.77) weeks)
- Rovalpituzumab Tesirine Antibody-Drug Conjugate Plasma Concentrations by Study Visit(Cycle 1: Day 1, 30 minutes pre-infusion; Day 1, 30 minutes post-infusion; Day 3; Day 15; Day 29. Cycle 2: Day 1, 30 minutes pre-infusion; Day 1, 30 minutes post-infusion; Day 3; Day 15; Day 29; End of Treatment (up to Day 29).)
- Number of Anti-Therapeutic Antibody (ATA) Positive Participants(up to 122.4 weeks; mean (SD) duration of follow-up was 29.0 (23.77) weeks)
- Number of Participants With Treatment-Related Adverse Events (TEAEs) During Initial Treatment(From first dose of study drug through the end of the initial treatment period (84 ± 6 days))
- Progression-Free Survival(up to 122.4 weeks; mean (SD) duration of follow-up was 29.0 (23.77) weeks)
- Number of Participants With TEAEs Occurring in at Least 10% of All Participants During Initial Treatment(From first dose of study drug through the end of the initial treatment period (84 ± 6 days))
研究者
相似试验
撤回
3 期
Study Evaluating the Safety of Rovalpituzumab Tesirine for Third-Line and Later Treatment of Subjects With Relapsed or Refractory Small Cell Lung CancerSmall Cell Lung CancerNCT03334487AbbVie
终止
1 期
A Study of Rovalpituzumab Tesirine Administered in Combination With Nivolumab and With or Without Ipilimumab for Adults With Extensive-Stage Small Cell Lung CancerSmall Cell Lung CancerNCT03026166AbbVie42
终止
1 期
A Study of Rovalpituzumab Tesirine (SC16LD6.5) in the Frontline Treatment of Patients With Extensive Stage Small Cell Lung CancerSmall Cell Lung CancerNCT02819999AbbVie28
已完成
3 期
A Study of Tislelizumab (BGB-A317) Versus Chemotherapy as Second Line Treatment in Participants With Advanced Esophageal Squamous Cell CarcinomaEsophageal Squamous Cell Carcinoma (ESCC)NCT03430843BeiGene512
终止
1 期
Rovalpituzumab Tesirine in Delta-Like Protein 3-Expressing Advanced Solid TumorsMalignant MelanomaMedullary Thyroid CancerLarge-Cell Neuroendocrine CarcinomaNeuroendocrine Prostate CancerHigh Grade Gastroenteropancreatic Neuroendocrine CarcinomaOther Neuroendocrine CarcinomaOther Solid TumorsGlioblastomaNCT02709889AbbVie200