Summary
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.
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Acknowledgements
We also acknowledge others instrumental in the preparation of this data and manuscript: Lada Keenan, Kathy McArthur, Zlatka Iamboliyska
Funding
This study was funded by Nereus Pharmaceuticals, Inc.
Disclosures
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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Millward, M., Mainwaring, P., Mita, A. et al. Phase 1 study of the novel vascular disrupting agent plinabulin (NPI-2358) and docetaxel. Invest New Drugs 30, 1065–1073 (2012). https://doi.org/10.1007/s10637-011-9642-4
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DOI: https://doi.org/10.1007/s10637-011-9642-4