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
Overview
- Phase
- Phase 2
- Intervention
- SHR-1210
- Conditions
- Small-cell Lung Cancer
- Sponsor
- Jiangsu HengRui Medicine Co., Ltd.
- Enrollment
- 59
- Locations
- 2
- Primary Endpoint
- Adverse Event
- Status
- Completed
- Last Updated
- last year
Overview
Brief Summary
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •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.
Exclusion Criteria
- •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.
Arms & Interventions
A (SHR-1210+Apatinib)
SHR-1210 200mg, IV, Q2W and Apatinib 375mg, PO, QD
Intervention: SHR-1210
A (SHR-1210+Apatinib)
SHR-1210 200mg, IV, Q2W and Apatinib 375mg, PO, QD
Intervention: Apatinib
B (SHR-1210+Apatinib)
SHR-1210 200mg, IV, Q2W and Apatinib 375mg, PO, QD (5 Days on, 2 Days off)
Intervention: SHR-1210
B (SHR-1210+Apatinib)
SHR-1210 200mg, IV, Q2W and Apatinib 375mg, PO, QD (5 Days on, 2 Days off)
Intervention: Apatinib
C (SHR-1210+Apatinib)
SHR-1210 200mg, IV, Q2W and Apatinib 375mg, PO, QD (7 Days on, 7 Days off)
Intervention: SHR-1210
C (SHR-1210+Apatinib)
SHR-1210 200mg, IV, Q2W and Apatinib 375mg, PO, QD (7 Days on, 7 Days off)
Intervention: Apatinib
Outcomes
Primary Outcomes
Adverse Event
Time Frame: 24 months
Evaluation of adverse event rate according to CTCAE v4.03
ORR
Time Frame: 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)
Secondary Outcomes
- 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.)