1686PD - Plinabulin (Plin), a novel non-G-CSF molecule for the revention of chemotherapy-induced neutropenia (CIN), has the potential to positively impact tumor micro environment

Abstract

Background: Elevated absolute neutrophil (N) count (ANC) may suppress the immune system and the activation of cytotoxic T-Lymphocytes (L). An elevated N-to-L Ratio (NLR) of NLR ≥ 5, is an independent negative prognostic indicator for outcome in cancer patients (pts) (Zhou; Nature 2017). CIN is a common side effect with chemo for which G-CSF is used. Plin is a novel small molecule in development for CIN caused by myelosuppressive chemos. Plin is given as a single IV infusion per cycle, 30 minutes after chemo, vs 24 hours after chemo with G-CSF. Plin does not cause bone pain. In contrast to G-CSF, Plin has anti-cancer, immune-enhancing activity due to dendritic cell activation and related T-cell proliferation (Mohanlal, ASCO-SITC 2018). We completed the Phase (Ph)2 portion of the Ph 2/3 Study BPI-2358-105 (NCT03102606), comparing Plin (at different doses; n = 55) head-to-head with Pegfilgrastim (Peg) for prevention of Docetaxel (Doc) CIN. Duration of Severe Neutropenia (DSN) and incidence of Grade 4 neutropenia (Gr 4 NP) in Cycle 1 were the same for Plin (20 mg/m2) and Peg (6 mg): 0.5 days and 14% resp for DSN and Gr 4 NP (Blayney, ASCO 2018). Since Plin and Peg both mitigate CIN, we examined the effect on NLR. Methods: The Ph2 portion of study 105 was analyzed for NLR in Cycle 1 from NSCLC pts receiving Doc with either Plin (20 mg/m2; n = 14) or Peg (6 mg; n = 14q5). ANC and L were available through day (D) 15. Results: Median ANC with Plin remained within normal range, whereas Peg induced an overshoot in ANC, exceeding upper limit of normal after D6 (p < 0.001). Peg, but not Plin, significantly increased NLR to a ratio of > 5 after D6.Table: 1686PDBaselineD6D7D8D9D10D15Plin NLR2.633.011.831.261.131.151.96Peg NLR4.113.935.098.319.2112.28.11P-value NLRNSNS0.03<0.001<0.001<0.001<0.001 Open table in a new tab Conclusions: Plin is an equally effective, single-dose-per cycle agent as Peg for CIN, however in contrast to Peg, Plin does not increase NLR to immune-suppressive levels, and has immune-enhancing activity. For Chemo/Immunotherapy combinations, Plin could be the preferred option to prevent CIN. Clinical trial identification: NCT03102606. Legal entity responsible for the study: BeyondSpring Pharmaceuticals, Inc. Funding: BeyondSpring Pharmaceuticals, Inc. Disclosure: D. Blayney: Leadership: Artelo Biosciences; Stock and other ownership interests: PRM Pharmaceutical, Artelo Biosciences Madorra; Consulting or advisory role: OnQ Cascadian Therapeutics, Varian Medical Systems, Mylan, Creare, Heron Oncology Learning Center; Research funding: Amgen, BeyondSpring Pharmaceuticals, S. Ogenstad: Employment: Anida Pharma, BeyondSpring Pharmaceuticals, Black Swan, Ferring Pharmaceuticals, A/S G&L Sciences, IMS; Expert services: Jenner & Block, PQ Bypass, Rubin, Anders, Scientific Sensible Medical Innovations Ltd, Shahin Gharakhanian, MD Consulting, LLC Somahlution, Inc, L. Du, L. Huang, R. Mohanlal: Employee of BeyondSpring Pharmaceuticals, Inc. All other authors have declared no conflicts of interest.