The plinabulin/docetaxel combination to mitigate the known safety concerns of docetaxel.

e20595 Background: Docetaxel is currently approved in non-small cell lung Cancer (NSCLC) after a failure of first line chemotherapy. However, docetaxel has an unfavorable toxicity profile that limits its use. A docetaxel-containing regimen with an improved safety profile would therefore be attractive. Plinabulin, a first-in-class small molecule vascular disruptive agent with potent immuno-oncology effects, is being developed in combination with docetaxel to address this need. Methods: We conducted a Phase 2 study comparing the safety and efficacy of the plinabulin /docetaxel combination (n=90) with docetaxel alone (n=73) in patients with NSCLC entering 2nd or 3rd line therapy. Plinabulin was given intravenously at 20 mg/m2 (n= 40) or 30 mg/m2 (n=50) and docetaxel at 75 mg/m2(n=73). Results: Efficacy results of this study were presented at ASCO 2014. Baseline characteristics for age, gender, ECOG performance score, histology and disease status were comparable between groups. The plinabulin/docetaxel combination improved overall survival, in a subset of patients with large tumors (> 3 cm; HR=0.758, p =0.36), and also had duration of response benefit over docetaxel alone (12.7 vs 1.5 months; P<0.05). We are reporting on the safety profile of plinabulin/ docetaxel combination. Conclusions: In this Phase 2 study, the plinabulin/docetaxel combination mitigated some of the docetaxel toxicities. Most importantly it improved docetaxel dose intensity. The neutropenia benefit was likely due to plinabulin-induced release of cytokines such as IL-1 and IL-6 (data obtained in in-vitro plinabulin studies), which are known to increase neutrophil count. In addition, preliminary results indicated a potential efficacy benefit of the plinabulin/docetaxel combination over docetaxel alone. A global Phase 3 trial with the plinabulin/docetaxel combination vs docetaxel alone is currently underway in the US, China, Australia and New Zealand. Clinical trial information: NCT00630110.Adverse events. Plinabulin/Docetaxel Docetaxel Grade 3/4 Neutropenia * 7 % 25 % Use of G-CSF * 14 % 29 % Sepsis 0 % 3.6 % Severe infections 0 % 3.6 % Asthenia * 13 % 28 % Docetaxel dose reduction due to toxicity * 6 % 20 % *p<0.01; Plinabulin/docetaxel combination vs docetaxel alone.