Clinical trial NCT03417895: SHR-1210 Combined With Apatinib in Treatment of ED-SCLC After Failure of First Line Standard Therapy
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Small-cell Lung Cancer
Lead sponsor: Jiangsu HengRui Medicine Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2018-01-31
Enrollment: 59
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

1. Signed inform consent form.
2. Age \>= 18 years and \<= 70 years.
3. Histologically or cytologically confirmed small cell lung cancer.
4. ED-SCLC according to Veterans Administration Lung Study Group.
5. Radiographically progression following a platinum-based standard prior chemotherapy regimen.
6. Eastern Cooperative Oncology Group performance status of 0 or 1.
7. Measurable disease as defined by RECIST v1.1.
8. Life expectancy \>= 8 weeks.
9. Adequate hematologic and end organ function.

Exclusion Criteria:

1. Histologically or cytologically confirmed mixed non-small cell and small cell carcinoma.
2. 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.
3. Prior exposure to anti-VEGF or anti-VEGFR therapy.
4. Active brain metastasis or meningeal metastasis.
5. Clinically significant third space effusion (e.g., uncontrolled pericardial effusion, ascites or pleural effusion by extraction or other treatment).
6. Known hypersensitivity to study drug or any of its excipients; known hypersensitivity to any antibody.
7. Treatment with any other investigational agent or participation in another clinical trial within 4 weeks prior to screening.
8. Other conditions that the investigator thinks unsuitable in this study.

Primary outcomes:
measure: Adverse Event
timeFrame: 24 months
measure: ORR
timeFrame: 6 months
Secondary outcomes:
measure: OS Rate
timeFrame: 6 months
measure: PFS
timeFrame: Imaging assessment was performed on C1D28 and every 8 weeks after C1D28 until radiographic progressive disease (PD) was documented.
measure: TTR
timeFrame: Imaging assessment was performed on C1D28 and every 8 weeks after C1D28 until radiographic progressive disease (PD) was documented.
measure: DoR
timeFrame: Imaging assessment was performed on C1D28 and every 8 weeks after C1D28 until radiographic progressive disease (PD) was documented.
measure: DCR
timeFrame: Imaging assessment was performed on C1D28 and every 8 weeks after C1D28 until radiographic progressive disease (PD) was documented.
measure: OS
timeFrame: on average of 2 years
Other outcomes:
Locations:
city: Beijing
country: China
facility: Cancer Hospital Chinese Academy of Medical Science
state: Beijing
city: Hangzhou
country: China
facility: Zhejiang Cancer Hospital
state: Zhejiang
Study officials:
affiliation: Jiangsu Hengrui Pharmaceutical Co., Ltd.
name: Wei Shi
role: STUDY_DIRECTOR
References:
citation: Fan Y, Zhao J, Wang Q, Huang D, Li X, Chen J, Fang Y, Duan J, Zhou C, Hu Y, Yang H, Hu Y, Zhou J, Lin X, Wang L, Wang Z, Xu Y, Zhang T, Shi W, Zou J, Wang J. Camrelizumab Plus Apatinib in Extensive-Stage SCLC (PASSION): A Multicenter, Two-Stage, Phase 2 Trial. J Thorac Oncol. 2021 Feb;16(2):299-309. doi: 10.1016/j.jtho.2020.10.002. Epub 2020 Nov 6.