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Investigational New Drugs

, Volume 36, Issue 2, pp 315–322 | Cite as

Phase III study of dulanermin (recombinant human tumor necrosis factor-related apoptosis-inducing ligand/Apo2 ligand) combined with vinorelbine and cisplatin in patients with advanced non-small-cell lung cancer

  • Xuenong Ouyang
  • Meiqi Shi
  • Fangwei Jie
  • Yuxian Bai
  • Peng Shen
  • Zhuang Yu
  • Xiuwen Wang
  • Cheng Huang
  • Min Tao
  • Zhehai Wang
  • Conghua Xie
  • Qi Wu
  • Yongqian Shu
  • Baohui Han
  • Fengchun Zhang
  • Yiping Zhang
  • Chunhong Hu
  • Xitao Ma
  • Yongjie Liang
  • Anlan Wang
  • Bing Lu
  • Yi Shi
  • Jinfei Chen
  • Zhixiang Zhuang
  • Jiejun Wang
  • Jianjin Huang
  • Changhui Wang
  • Chunxue Bai
  • Xin Zhou
  • Qiang Li
  • Feng Chen
  • Hao Yu
  • Jifeng Feng
PHASE III STUDIES
  • 295 Downloads

Summary

Background Dulanermin is a recombinant soluble human Apo2 ligand/tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) that activates apoptotic pathways by binding to proapoptotic death receptor (DR) 4 and DR5. The purpose of this study was to evaluate the efficacy and safety of dulanermin combined with vinorelbine and cisplatin (NP) as the first-line treatment for patients with advanced non-small-cell lung cancer (NSCLC). Experimental design Patients were randomly assigned to receive NP chemotherapy (vinorelbine 25 mg/m2 on days 1 and 8 and cisplatin 30 mg/m2 on days 2 to 4) for up to six cycles plus dulanermin (75 μg/kg on days 1 to 14) or placebo every three weeks until disease progression, intolerable toxicity, or withdrawal of consent. The primary end point was progression-free survival (PFS), and the secondary end points included objective response rate (ORR), overall survival (OS), and safety evaluation. Results Between October 2009 and June 2012, 452 untreated patients with stage IIIB to IV NSCLC were randomly assigned to receive dulanermin plus NP (n = 342) and placebo plus NP (n = 110). Median PFS was 6.4 months in the dulanermin arm versus 3.5 months in the placebo arm (hazard ratio (HR), 0.4034; 95% CI, 0.3181 to 0.5117, p < 0.0001). ORR was 46.78% in the dulanermin arm versus 30.00% in the placebo arm (p = 0.0019). Median OS was 14.6 months in the dulanermin arm versus 13.9 months in the placebo arm (HR, 0.94; 95% CI, 0.74 to 1.21, p = 0.64). The most common grade ≥ 3 adverse events (AEs) were oligochromemia, leukopenia, neutropenia, and oligocythemia. Overall incidence of AEs, grade ≥ 3 AEs, and serious AEs were similar across the two arms. Conclusion Addition of dulanermin to the NP regimen significantly improved PFS and ORR. However, our results showed that the combination of dulanermin with chemotherapy had a synergic activity and favorable toxic profile in the treatment of patients with advanced NSCLC.

Keywords

Phase III Dulanermin NSCLC Progression-free survival Objective response rate 

Notes

Acknowledgements

The authors thank the patients who participated in this study and express appreciation of the assistance and understanding of their families. The authors also thank the study-site staff for their support.

Funding

The work was also funded by Shanghai Biomedical Technology fund (grant number 08431901100), National Innovation Fund (grant number 10C26213100701), and National Science and Technology Major Project fund (grant number 2010ZX09401-301).

Compliance with ethical standards

Conflict of interest

All authors received research funding from Gebaide Biotechnology Co., Ltd. for conducting the study and preparing this report. No potential conflicts of interest were disclosed.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Written informed consent was obtained from all individual patients included in the study.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2017

Authors and Affiliations

  • Xuenong Ouyang
    • 1
  • Meiqi Shi
    • 2
  • Fangwei Jie
    • 1
  • Yuxian Bai
    • 3
  • Peng Shen
    • 4
  • Zhuang Yu
    • 5
  • Xiuwen Wang
    • 6
  • Cheng Huang
    • 7
  • Min Tao
    • 8
  • Zhehai Wang
    • 9
  • Conghua Xie
    • 10
  • Qi Wu
    • 11
  • Yongqian Shu
    • 12
  • Baohui Han
    • 13
  • Fengchun Zhang
    • 14
  • Yiping Zhang
    • 15
  • Chunhong Hu
    • 16
  • Xitao Ma
    • 17
  • Yongjie Liang
    • 18
  • Anlan Wang
    • 19
  • Bing Lu
    • 20
  • Yi Shi
    • 21
  • Jinfei Chen
    • 22
  • Zhixiang Zhuang
    • 23
  • Jiejun Wang
    • 24
  • Jianjin Huang
    • 25
  • Changhui Wang
    • 26
  • Chunxue Bai
    • 27
  • Xin Zhou
    • 28
  • Qiang Li
    • 29
  • Feng Chen
    • 30
  • Hao Yu
    • 30
  • Jifeng Feng
    • 2
  1. 1.Department of Medical Oncology, Fuzhou General Hospital of Nanjing Military Command, Fuzong Clinical CollegeFujian Medical UniversityFuzhouChina
  2. 2.Department of Medical OncologyJiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing Medical University affiliated Cancer HospitalNanjingChina
  3. 3.Department of Gastrointestinal OncologyThe Third Affiliated Hospital, Harbin Medical UniversityHarbinChina
  4. 4.Department of Medical OncologyFirst Affiliated Hospital, Zhejiang University School of MedicineHangzhouChina
  5. 5.Department of OncologyThe Affiliated Hospital of Qingdao UniversityQingdaoChina
  6. 6.Department of ChemotherapyQilu Hospital of Shandong UniversityJinanChina
  7. 7.Department of Medical OncologyFujian Provincial Cancer Hospital, The Teaching Hospital of Fujian Medical University, The Teaching Hospital of Fujian University of Traditional Chinese MedicineFuzhouChina
  8. 8.Department of OncologyThe First Affiliated Hospital of Soochow UniversitySuzhouChina
  9. 9.Department of internal Medicine-OncologyShandong Cancer Hospital and Institute, Shandong Cancer Hospital affiliated to Shandong University, Shandong Academy of Medical SciencesJinanChina
  10. 10.Department of Radiation and Medical OncologyZhongnan Hospital of Wuhan UniversityWuhanChina
  11. 11.Department of OncologySichuan Academy of Medical Sciences & Sichuan Provincial People’s HospitalChengduChina
  12. 12.Department of OncologyJiangsu Proving Hospital, The First Affiliated Hospital of Nanjing Medical UniversityNanjingChina
  13. 13.Department of Pulmonary MedicineShanghai Chest Hospital, Shanghai Jiao Tong UniversityShanghaiChina
  14. 14.Department of OncologyRenji Hospital Shanghai Jiao Tong University School of MedicineShanghaiChina
  15. 15.Department of Medical OncologyZhejiang Cancer HospitalZhejiangChina
  16. 16.Department of OncologyThe Second Xiangya Hospital of Central South UniversityChangshaChina
  17. 17.Department of Respiratory and Critical Care MedicineHenan Provincial People’s HospitalZhengzhouChina
  18. 18.Department of Respiratory MedicineShanghai East Hospital, Tongji UniversityShanghaiChina
  19. 19.Department of Medical OncologyHunan Cancer HospitalChangshaChina
  20. 20.Department of Respiratory MedicineShanghai Pulmonary Hospital, Tongji University School of MedicineShanghaiChina
  21. 21.Department of Respiratory MedicineNanjing General Hospital of Nanjing Military CommandNanjingChina
  22. 22.Department of OncologyNanjing First Hospital, Nanjing Medical UniversityNanjingChina
  23. 23.Department of OncologyThe Second Affiliated Hospital of Soochow UniversitySuzhouChina
  24. 24.Department of Medical OncologyChangzheng HospitalShanghaiChina
  25. 25.Department of Medical OncologyThe Second Affiliated Hospital of Zhejiang University School of MedicineHangzhouChina
  26. 26.Department of Respiratory MedicineShanghai Tenth People’s Hospital, Tongji UniversityShanghaiChina
  27. 27.Department of Respiratory MedicineZhongshan Hospital Affiliated to Fudan UniversityShanghaiChina
  28. 28.Department of RespiratoryShanghai General Hospital, Shanghai Jiao Tong University School of MedicineShanghaiChina
  29. 29.Department of Respiratory MedicineChanghai Hospital, The Second Military Medical UniversityShanghaiChina
  30. 30.Department of Epidemiology and Biostatistics, School of Public HealthNanjing Medical UniversityNanjingChina

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