SHR-1210 Combined With Apatinib in Treatment of ED-SCLC After Failure of First Line Standard Therapy

Study Overview
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Brief Summary
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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.

Detailed Description
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Subjects will be 1:1:1 randomly assigned to receive SHR-1210 200mg, IV, Q2W and Apatinib 375mg, PO, QD, or SHR-1210 200mg, IV, Q2W and Apatinib 375mg, PO, QD（5 Days on, 2 Days off）, or SHR-1210 200mg, IV, Q2W and Apatinib 375mg, PO, QD（7 Days on, 7 Days off） treatment until disease progression, unacceptable toxicity, or death.

Official Title
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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

Conditions
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Small-cell Lung Cancer

Intervention / Treatment
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* Drug: SHR-1210
* Drug: Apatinib


Participation Criteria
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Eligibility Criteria
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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 1 Measurable disease as defined by RECIST v1.1 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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A(SHR-1210+Apatinib)<br>• SHR-1210 200mg, IV, Q2W and Apatinib 375mg, PO, QD | Drug: SHR-1210<br>* A humanized anti-PD-1 monoclonal antibody<br>Drug: Apatinib<br>* A tyrosine kinase inhibitor selectively targeting VEGFR-2<br>|
| Experimental: B(SHR-1210+Apatinib)<br>• SHR-1210 200mg, IV, Q2W and Apatinib 375mg, PO, QD（5 Days on, 2 Days off） | Drug: SHR-1210<br>* A humanized anti-PD-1 monoclonal antibody<br>Drug: Apatinib<br>* A tyrosine kinase inhibitor selectively targeting VEGFR-2<br>|
| Experimental: C(SHR-1210+Apatinib)<br>• SHR-1210 200mg, IV, Q2W and Apatinib 375mg, PO, QD（7 Days on, 7 Days off） | Drug: SHR-1210<br>* A humanized anti-PD-1 monoclonal antibody<br>Drug: Apatinib<br>* A tyrosine kinase inhibitor selectively targeting VEGFR-2<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse event of part 1 | • Evaluation of adverse event rate according to CTCAE v4.03 | on average of of 3 months(First 6 subjects in each arm) | 
| ORR | • Objective response rate according to RECIST v1.1 | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse event | • Evaluation of adverse event rate according to CTCAE v4.03 | 6 months | 
| OS rate | • OS rate | 6 months | 
| PFS | • Progression-free survival according to RECIST v1.1 | 6 months | 
| TTR | • Time to response according to RECIST v1.1 | 6 months | 
| DoR | • Duration of response according to RECIST v1.1 | 6 months | 
| DCR | • Disease control rate according to RECIST v1.1 | 6 months | 
| OS | • Overall survival | on average of 2 years | 
| Immunogenicity | • Positive rate of anti-drug antibody and neutralizing antibody | 6 months |