Background: Plinabulin (Plin) is a small molecule with anti-cancer activity and CIN effects. The Phase (Ph) 2 clinical trial NPI-2358-101 ( NCT00630110 ) evaluated Plin at 20 or 30 mg/m2 on Day (D) 1 and D8) plus D1 Docetaxel (Doc) 75 mg/m2 combination versus D1 Doc alone in patients (pts) with non-small cell lung cancer(NSCLC). In a large ( > 70%) subset of pts with a measurable lung lesion in the lung (per RECIST 1.1) receiving 30 mg/m2 Plin + Doc (n = 38), mOS was 4.6 months longer vs Doc alone (n = 38) (Mohanlal ASCO-SITC 2018). An unexpected post-hoc finding was a CIN benefit with adding at 20 or 30 mg/m2 Plin to Doc: 33% of pts in the Doc arm had grade 4 neutropenia, whereas in the Plin +Doc group 4% of pts (P < 0.0003) (Blayney ASH 2018). Plin boost the number the number of hematopoietic/progenitor cells in bone marrow. We subsequently initiated two global Ph3 programs with Plin: 1. A Ph 3 trial confirming its anticancer activity in NSCLC (study BPI-2358-103; NCT02504489; this trial is ongoing) and 2. An evaluation of Plin for CIN prevention through studies BPI-2358-105 (NCT03102606; PROTECTIVE-1), and study 106 (NCT03294577; PROTECTIVE-2). We previously reported from the Ph 2 portion of study 105, that SA Plin and Pegfigrastim (Peg) had comparable protection against CIN induced by Doc, however in contrast to Peg, Plin did not cause bone pain or thrombocytopenia (Blayney IASLC 2018, ESMO 2018). Plin is given by 30 min IV infusion on the same day of Chemo, 30 min after Chemo. The Ph3 portion of Study 105 in ongoing. Methods: In the Ph 3 portion of PROTECTIVE-1, pts with NSCLC, HRPC or BC are randomized (1:1) to either Plin 40 mg (over 30 minutes on D1; n = 75) or Peg 6mg (on D2, n = 75), and the primary endpoint is Duration of Severe Neutropenia (DSN). Plin 20 mg/m2 is similar to a 40 mg fixed dose. Absolute neutrophil counts (ANC) is determined on D 0, 1,2,3,6,8,9,10, 15 in Cycle 1 The trial aims to demonstrate non-inferiority of Plin vs Peg. Non-inferiority will be declared if the non-inferiority margin (NIM) of 0.65 day will be met, which NIM is more conservative than the 1 day NIM, typically employed for G-CSG biosimilar trials. Pts should have at least 1 risk factor as per NCCN guidelines.The trial is double-blinded to enable reliable PRO, Bone Pain and QoL assessments through validated questionnaires (EQ-5D-5L; EORTC QLQ-C30; Wang Baker Faces Pain Rating Scale). Following an Interim Analysis, the trial will continue without modifications. Clinical trial information: NCT03102606.