Efficacy of Plinabulin vs Pegfilgrastim for Prevention of Chemotherapy-Induced Neutropenia in Adults With Non-Small Cell Lung Cancer A Phase 2 Randomized Clinical Trial

IMPORTANCE Plinabulin is a novel, non-granulocyte colony-stimulating factor (GCSF) small molecule with both anticancer and neutropenia-prevention effects. OBJECTIVE To assess the efficacy and safety of plinabulin compared with pegfilgrastim for the prevention of chemotherapy-induced neutropenia following docetaxel chemotherapy in patients with non-small lung cancer. DESIGN, SETTING, AND PARTICIPANTS This was a randomized, open-label, phase 2 clinical trial of 4 treatment arms that was conducted in 19 cancer treatment centers in the United States, China, Russia, and Ukraine. Participants were adult patients with non-small cell lung cancer whose cancer had progressed after platinum-based chemotherapy. Data were collected from April 2017 through March 2018 and analyzed from August 2019 through February 2020. INTERVENTIONS All patients received docetaxel 75mg/m(2) on day 1 and were randomly assigned to 1 of 3 doses of plinabulin (5, 10, or 20mg/m(2)) on day 1 or to pegfilgrastim 6mg on day 2. Patients were treated every 21 days for 4 chemotherapy cycles. MAIN OUTCOMES AND MEASURES The primary end point was the determination of the recommended phase 3 dose of plinabulin based on the days of severe neutropenia during chemotherapy cycle 1. Daily complete blood cell counts and absolute neutrophil counts were drawn during times of anticipated neutropenia during cycle 1. RESULTS Of the 55 patients randomized and evaluated, the mean (SD) age was 61.3 (10.2) years, and 38 (69.1%) were men. With each escalation of the plinabulin dose, the incidence of any grade of neutropenia decreased. There were no significant differences in mean (SD) days of severe neutropenia among those treated with pegfilgrastim (0.15 [0.38] days) when dosed at day 2 vs plinabulin 20mg/m(2) (0.36 [0.93] days; P=.76) when dosed at day 1, and no safety signals were detected. CONCLUSIONS AND RELEVANCE Single dose-per-cycle plinabulin has a similar neutropenia protection benefit as pegfilgrastim. Plinabulin 40mg fixed dose, which is pharmacologically equivalent to 20mg/m(2), will be compared with pegfilgrastim 6mg in the phase 3 portion of this trial. Noninferior days of severe neutropenia will be the primary end point, and bone pain reduction, thrombocytopenia reduction, and quality of life maintenance will be secondary end points.