Anti-PD-1 Antibody SHR-1210 Combined With Anti-angiogenesis Inhibitor Apatinib in Treatment of Extensive-stage Disease Small Cell Lung Cancer After Failure of First Line Standard Therapy
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 59
- 试验地点
- 2
- 主要终点
- Adverse Event
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 one dose (375mg). Comparison of 3 different dose schedules in subjects with extensive-stage disease small cell lung cancer. 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).
The study is composed of two parts. Part 1 of the study will determine the safety and tolerability of SHR-1210 in combination with Apatinib in first 6 subjects of each arm. The second phase of treatment was carried out by selecting one group of administration mode and the tolerated dose of Apatinib. Part 2 of the study will determine the safety and efficacy of SHR-1210 in combination with Apatinib in 39 subjects.
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
- •Signed inform consent form.
- •Age >= 18 years and <= 70 years.
- •Histologically or cytologically confirmed small cell lung cancer.
- •ED-SCLC according to Veterans Administration Lung Study Group.
- •Radiographically progression following a platinum-based standard prior chemotherapy regimen.
- •Eastern Cooperative Oncology Group performance status of 0 or
- •Measurable disease as defined by RECIST v1.
- •Life expectancy >= 8 weeks.
- •Adequate hematologic and end organ function.
排除标准
- •Histologically or cytologically confirmed mixed non-small cell and small cell carcinoma.
- •Prior exposure to therapeutic anticancer vaccines; prior exposure to any T cell co-stimulatory therapy or immune checkpoint inhibitors, including but not limited to other anti-CTLA-4, anti-PD-1, anti-PD-L1 and anti-PD-L2 antibodies.
- •Prior exposure to anti-VEGF or anti-VEGFR therapy.
- •Active brain metastasis or meningeal metastasis.
- •Clinically significant third space effusion (e.g., uncontrolled pericardial effusion, ascites or pleural effusion by extraction or other treatment).
- •Known hypersensitivity to study drug or any of its excipients; known hypersensitivity to any antibody.
- •Treatment with any other investigational agent or participation in another clinical trial within 4 weeks prior to screening.
- •Other conditions that the investigator thinks unsuitable in this study.
研究组 & 干预措施
A (SHR-1210+Apatinib)
SHR-1210 200mg, IV, Q2W and Apatinib 375mg, PO, QD
干预措施: SHR-1210 (Drug)
A (SHR-1210+Apatinib)
SHR-1210 200mg, IV, Q2W and Apatinib 375mg, PO, QD
干预措施: Apatinib (Drug)
B (SHR-1210+Apatinib)
SHR-1210 200mg, IV, Q2W and Apatinib 375mg, PO, QD (5 Days on, 2 Days off)
干预措施: SHR-1210 (Drug)
B (SHR-1210+Apatinib)
SHR-1210 200mg, IV, Q2W and Apatinib 375mg, PO, QD (5 Days on, 2 Days off)
干预措施: Apatinib (Drug)
C (SHR-1210+Apatinib)
SHR-1210 200mg, IV, Q2W and Apatinib 375mg, PO, QD (7 Days on, 7 Days off)
干预措施: SHR-1210 (Drug)
C (SHR-1210+Apatinib)
SHR-1210 200mg, IV, Q2W and Apatinib 375mg, PO, QD (7 Days on, 7 Days off)
干预措施: Apatinib (Drug)
结局指标
主要结局
Adverse Event
时间窗: 24 months
Evaluation of adverse event rate according to CTCAE v4.03
ORR
时间窗: 6 months
Objective response rate according to RECIST v1.1 (Response was assessed with CT or MRI using RECIST v1.1, Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to\<10 mm; Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Over all response：CR+PR)
次要结局
- OS(on average of 2 years)
- PFS(Imaging assessment was performed on C1D28 and every 8 weeks after C1D28 until radiographic progressive disease (PD) was documented.)
- DCR(Imaging assessment was performed on C1D28 and every 8 weeks after C1D28 until radiographic progressive disease (PD) was documented.)
- OS Rate(6 months)
- TTR(Imaging assessment was performed on C1D28 and every 8 weeks after C1D28 until radiographic progressive disease (PD) was documented.)
- DoR(Imaging assessment was performed on C1D28 and every 8 weeks after C1D28 until radiographic progressive disease (PD) was documented.)