Investigational New Drugs

, Volume 30, Issue 3, pp 1065–1073 | Cite as

Phase 1 study of the novel vascular disrupting agent plinabulin (NPI-2358) and docetaxel

  • Michael Millward
  • Paul Mainwaring
  • Alain Mita
  • Kristine Federico
  • G. K. Lloyd
  • Natasha Reddinger
  • Steffan Nawrocki
  • Monica Mita
  • Matthew A. Spear


Background Plinabulin (NPI-2358) is a vascular disrupting agent (VDA) that destabilizes tumor vascular endothelial cell architecture resulting in selective collapse of established tumor vasculature producing anti-tumor activity alone or in combination with cytotoxic agents. The objective of this study was to assess the recommended Phase 2 dose (RP2D) of plinabulin combined with docetaxel. Patients and Methods Patients received 75 mg/m2 docetaxel on day 1 and plinabulin on days 1 and 8 intravenously in 21 day cycles. Plinabulin was escalated from the biologically effective dose (BED) of 13.5 mg/m2 to the standard single agent dose of 30 mg/m2 using a “3+3” design. Results Thirteen patients were enrolled. Adverse events were consistent with those of both agents alone. Fatigue, pain, nausea, diarrhea and vomiting were the most common events. One dose limiting toxicity of nausea, vomiting, dehydration and neutropenia occurred. The RP2D was 30 mg/m2 of plinabulin with 75 mg/m2 docetaxel. Pharmacokinetics did not indicate drug-drug interactions. Of the 8 patients with NSCLC evaluable for response, 2 achieved a partial response and 4 demonstrated lesser decreases in tumor measurements. Conclusions The combination of full doses of plinabulin and docetaxel is tolerable. With encouraging antitumor activity, this supported further development of this combination.


Angiogenesis Docetaxel Non-small cell lung cancer (NSCLC) Vascular disrupting agent (VDA) Vascular targeting 



We also acknowledge others instrumental in the preparation of this data and manuscript: Lada Keenan, Kathy McArthur, Zlatka Iamboliyska


This study was funded by Nereus Pharmaceuticals, Inc.


The following authors declare a conflict of interest on the basis that they are full-time employees of Nereus Pharmaceuticals: MAS, KCF, GKL, NR. The following authors have received meeting travel reimbursement: MM, PM, ACM, MMM. The following authors have received honoraria: MM, PM, MMM. The following authors are or have conducted research sponsored by Nereus Pharmaceuticals: MM (this and/or other clinical trials), PM (this and/or other clinical trials), ACM (this and/or other clinical trials), MMM (this and/or other clinical trials), SN (laboratory studies on plinabulin).


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Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Michael Millward
    • 1
  • Paul Mainwaring
    • 2
    • 5
  • Alain Mita
    • 3
  • Kristine Federico
    • 4
  • G. K. Lloyd
    • 4
  • Natasha Reddinger
    • 4
  • Steffan Nawrocki
    • 3
  • Monica Mita
    • 3
  • Matthew A. Spear
    • 4
  1. 1.Department of Medical OncologySir Charles Gairdner Hospital & University of Western AustraliaPerthAustralia
  2. 2.Division of Cancer ServicesMater HospitalBrisbaneAustralia
  3. 3.Cancer Therapy and Research CenterInstitute for Drug DevelopmentSan AntonioUSA
  4. 4.Nereus Pharmaceuticals, IncSan DiegoUSA
  5. 5.Haematology and Oncology Clinics of AustraliaBrisbaneAustralia

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