A Study of Rovalpituzumab Tesirine (SC16LD6.5) in the Frontline Treatment of Patients With Extensive Stage Small Cell Lung Cancer
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- 入组人数
- 28
- 试验地点
- 10
- 主要终点
- Dose limiting toxicities (DLT) of rovalpituzumab tesirine when administered as monotherapy, in series or in combination with frontline chemotherapy to subjects with DLL3 expressing extensive-stage small cell lung cancer (SCLC)
研究概览
简要总结
The purpose of the study is to test the effect of rovalpituzumab tesirine in the frontline treatment of small cell lung cancer (SCLC).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 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
- •Age ≥ 18 years with histologically- or cytologically-confirmed, extensive-stage, chemotherapy-naïve SCLC
- •DLL3-expressing SCLC based on central immunohistochemistry (IHC) assessment. Positive is defined as staining in ≥75% of tumor cells.
- •Eastern Cooperative Oncology Group performance status of 0 or
- •Minimum life expectancy of at least 12 weeks.
- •Recovery to Grade 1 of any clinically significant toxicity (excluding alopecia) prior to initiation of study drug.
- •Satisfactory laboratory parameters within defined parameters (ANC, platelet count, Hb, total bilirubin, ALT, AST and GFR)
- •Subjects with a history of CNS metastases must have completed definitive treatment prior to first dose of study treatment, off or on a stable dose of corticosteroids
- •Use of effective contraception method during and for 1 year following study drug dosing if female of childbearing potential or sexually active male
排除标准
- •Prior systemic chemotherapy, small molecule inhibitors, immune checkpoint inhibitors, other monoclonal antibodies, antibody-drug conjugates, radioimmunoconjugates, T-cell or other cell-based or biologic therapies, or any other anticancer therapy for the treatment of (limited or extensive) SCLC.
- •Any significant medical condition, that, in the opinion of the investigator or sponsor, may place the subject at undue risk from the study.
- •Documented history of a cerebral vascular, 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.
- •Women who are pregnant or breastfeeding.
- •History of another invasive malignancy that has not been in remission for at least 3 years. Exceptions: 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
研究组 & 干预措施
Rovalpituzumab Tesirine
Rovalpituzumab Tesirine 0.3 mg/kg IV infusion
干预措施: Rovalpituzumab Tesirine (Drug)
Rovalpituzumab Tesirine followed by Cisplatin, Etoposide
Rovalpituzumab Tesirine 0.3 mg/kg IV infusion followed by Cisplatin 80 mg/m2 and Etoposide 100 mg/m2 IV infusion
干预措施: Rovalpituzumab Tesirine (Drug)
Rovalpituzumab Tesirine followed by Cisplatin, Etoposide
Rovalpituzumab Tesirine 0.3 mg/kg IV infusion followed by Cisplatin 80 mg/m2 and Etoposide 100 mg/m2 IV infusion
干预措施: Cisplatin (Drug)
Rovalpituzumab Tesirine followed by Cisplatin, Etoposide
Rovalpituzumab Tesirine 0.3 mg/kg IV infusion followed by Cisplatin 80 mg/m2 and Etoposide 100 mg/m2 IV infusion
干预措施: Etoposide (Drug)
Rovalpituzumab Tesirine with Cisplatin, Etoposide
Cisplatin 80 mg/m2 and Etoposide 100 mg/m2 IV infusion and Rovalpituzumab Tesirine 0.1 mg/kg IV infusion
干预措施: Rovalpituzumab Tesirine (Drug)
Rovalpituzumab Tesirine with Cisplatin, Etoposide
Cisplatin 80 mg/m2 and Etoposide 100 mg/m2 IV infusion and Rovalpituzumab Tesirine 0.1 mg/kg IV infusion
干预措施: Cisplatin (Drug)
Rovalpituzumab Tesirine with Cisplatin, Etoposide
Cisplatin 80 mg/m2 and Etoposide 100 mg/m2 IV infusion and Rovalpituzumab Tesirine 0.1 mg/kg IV infusion
干预措施: Etoposide (Drug)
Rovalpituzumab Tesirine following Cisplatin, Etoposide
Cisplatin 80 mg/m2 and Etoposide 100 mg/m2 IV infusion followed by Rovalpituzumab Tesirine 0.3 mg/kg IV infusion
干预措施: Rovalpituzumab Tesirine (Drug)
Rovalpituzumab Tesirine following Cisplatin, Etoposide
Cisplatin 80 mg/m2 and Etoposide 100 mg/m2 IV infusion followed by Rovalpituzumab Tesirine 0.3 mg/kg IV infusion
干预措施: Cisplatin (Drug)
Rovalpituzumab Tesirine following Cisplatin, Etoposide
Cisplatin 80 mg/m2 and Etoposide 100 mg/m2 IV infusion followed by Rovalpituzumab Tesirine 0.3 mg/kg IV infusion
干预措施: Etoposide (Drug)
结局指标
主要结局
Dose limiting toxicities (DLT) of rovalpituzumab tesirine when administered as monotherapy, in series or in combination with frontline chemotherapy to subjects with DLL3 expressing extensive-stage small cell lung cancer (SCLC)
时间窗: within 21 days after first dose of rovalpituzumab tesirine
For Phase 1a
Treatment emergent adverse events (TEAEs)
时间窗: through 30 days after last dose of study treatment
For Phase 1a
Incidence of subjects with CTCAE Grade >2 laboratory abnormalities
时间窗: through 30 days after last dose of study treatment
For Phase 1a
Progression-Free Survival (PFS)
时间窗: 4 years
For Phase 1b
次要结局
- Best overall response rate(4 years)
- Duration of response (DOR)(4 years)
- Clinical Benefit Rate (CBR)(4 years)
- Overall Survival (OS)(4 years)
- Incidence of anti-therapeutic antibodies (ATAs) against rovalpituzumab tesirine(4 years)
- Progression-free survival (Phase 1a)(4 years)
- Pharmacokinetic parameters: Cmax (Maximum plasma concentration observed )(4 years)
- Pharmacokinetic parameters: AUC0-tau (Area under the plasma concentration-time curve within a dosing interval)(4 years)
- Pharmacokinetic parameters: AUC0-∞ (Area under the curve from time 0 extrapolated to infinity)(4 years)
- Pharmacokinetic parameters: Tmax (Time of Cmax)(4 years)
- Pharmacokinetic parameters: Ctrough (Observed plasma concentrations at trough)(4 years)
- Pharmacokinetic parameters: T1/2 (Terminal half-life)(4 years)
- Pharmacokinetic parameters: CL (Clearance)(4 years)
- Pharmacokinetic parameters: Vss (Volume of distribution at steady state)(4 years)
- Incidence of TEAEs(4 years)
- Changes in vital signs (Heart Rate)(4 years)
- Changes in vital signs (Blood pressure)(4 years)
- Changes in vital signs (Temperature)(4 years)
- Changes in vital signs (Weight)(4 years)
- Changes in vital signs (Respirations)(4 years)
- Eastern Cooperative Oncology Group (ECOG) score(4 years)