A Phase II Study of SHR-1210 in Combination With Apatinib in Advanced Non-Small Cell Lung
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 210
- 试验地点
- 1
- 主要终点
- Incidence and Grade of Adverse Events (AEs) and Serious Adverse Events (SAEs)
研究概览
简要总结
This is a multi-center, open-label, Phase II study of intravenous (IV) SHR-1210 at 200mg, q2w in combination with Apatinib at two dose levels in subjects with locally advanced or metastatic non-small cell lung cancer (NSCLC).
The study is composed of two parts. Part 1 of the study will determine the safety, tolerability and pharmacokinetics of SHR-1210 in combination with Apatinib.
Part 2 includes a randomized comparison of Apatinib 250mg/d or 500mg/d plus SHR-1210.
Subject's tumors will be screened at baseline for EGFR mutations, EML4-ALK translocation, and PD-L1 expression.But positive tumor PD-L1 expression will not be required for enrollment.
详细描述
SHR-1210 is a humanized monoclonal antibody against Programmed death 1(PD-1). Apatinib is a new kind of selective Vascular Endothelial Growth Factor Receptor 2(VEGFR-2) tyrosine kinase inhibitor (TKI). A disease-control rate of 61.1% and a mPFS of 4.7 months were showed in Apatinib phase II study in patients with NSCLC.
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 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subjects >/= 18 years and </=70 years of age at the time of Informed Consent.
- •Advanced relapsed or refractory predominantly NSCLC with at least one measurable lesion according to RECIST 1.
- •Failure of second line of chemotherapy(Part 1); Failure of First line of chemotherapy(Part 2)
- •Eastern Cooperative Oncology Group (ECOG) performance status 0-
- •Patients must have recovered from any AEs of prior treatments before randomization.
- •Adequate bone marrow,liver and renal function as assessed by the following laboratory tests conducted within 1 week before randomization. HB ≥ 90g/L; ANC≥1.5×10E+9/L; PLT≥100×10E+9/L; ALT and AST < 1.5×ULN; TBIL ≤1×ULN; Cr ≤1.5×ULN or CL≥60 ml/min.
- •Life expectancy of at least three months.
- •Male or female participants of childbearing potential must be willing to use an adequate method of contraception starting with the first dose of study drug through 60 days for female subjects and 120 days for male subjects after the last dose of study drug.
- •Written informed consent and the willingness and ability to comply with all aspects of the protocol.
排除标准
- •Suffered from grade II or above myocardial ischemia or myocardial infarction, uncontrolled arrhythmias (including QT interval male ≥ 450 ms, female≥ 470 ms).
- •Severe or uncontrolled systemic disease such as clinically significant hypertension (systolic pressure >/= 140 mm Hg and/or diastolic pressure >/= 90 mm Hg), and Grade III-IV cardiac insufficiency, according to NYHA criteria or echocardiography check: LVEF<50%.
- •Factors to affect oral administration (inability to swallow tablets,GI tract resection, chronic bacillary diarrhea and intestinal obstruction).
- •Coagulation disfunction,hemorrhagic tendency or receiving anticoagulant therapy
- •>/= CTCAE 2 pneumorrhagia or >/= CTCAE 3 hemorrhage in other organs within 4 weeks.
- •Bone fracture or wounds that was not cured.
- •Arterial thrombus or phlebothrombosis within 6 months and taking anticoagulant agents.
- •Mental diseases and psychotropic substances abuse.
- •Previous treatment with an trial agent within 4 weeks
- •Proteinuria ≥ (++) or 24 hours total urine protein > 1.0 g.
- •Other coexisting malignant disease (except basal-cell carcinoma and carcinoma in situ of uterine cervix).
研究组 & 干预措施
SHR-1210，200mg,q2w plus apatinib 500mg/d
SHR-1210 200mg, IV, Q2W and Apatinib 500mg, PO, QD
干预措施: Apatinib (Drug)
SHR-1210，200mg,q2w plus apatinib 250mg/d
SHR-1210 200mg, IV, Q2W and Apatinib 250mg, PO, QD
干预措施: SHR-1210 (Biological)
SHR-1210，200mg,q2w plus apatinib 250mg/d
SHR-1210 200mg, IV, Q2W and Apatinib 250mg, PO, QD
干预措施: Apatinib (Drug)
SHR-1210，200mg,q2w plus apatinib 500mg/d
SHR-1210 200mg, IV, Q2W and Apatinib 500mg, PO, QD
干预措施: SHR-1210 (Biological)
SHR-1210，200mg,q2w plus apatinib 375mg/d
SHR-1210 200mg, IV, Q2W and Apatinib 375mg, PO, QD
干预措施: SHR-1210 (Biological)
SHR-1210，200mg,q2w plus apatinib 375mg/d
SHR-1210 200mg, IV, Q2W and Apatinib 375mg, PO, QD
干预措施: Apatinib (Drug)
结局指标
主要结局
Incidence and Grade of Adverse Events (AEs) and Serious Adverse Events (SAEs)
时间窗: from signing the informed consent form to safety follow-up, 61 months
Number of participants with Adverse Events and Serious Adverse Events
Objective Response Rate (ORR)：
时间窗: from first administration to progressive disease or initiation of new anti-cancer therapy, 61 months
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
次要结局
未报告次要终点