Background: Peg is the current standard of care (SoC) for the prevention of CIN, with a low absolute neutrophil (N) count (ANC) week 1 after chemotherapy (chemo) with normalization in week 2. Breakthrough designation agent from FDA, Plin, a novel, non-G-CSF agent for the prevention of CIN, produces a normal ANC in week 1 of cycle (C) 1 by potentially protecting progenitor cells in bone marrow from chemo assault, and also has anticancer activity (Blayney, St Gallen 2019; ASCO 2019). Here we report data from a pre-specified interim analysis from PROTECTIVE-1 (Study 105; NCT03102606). Methods: Breast cancer (BC), lung (NSCLC) and prostate cancer (HRPC) pts with at least 1 risk factor as per NCCN, received docetaxel (Doc) 75 mg/m2 with either Peg 6mg (n=53) or Plin 40 mg (n=52) over 4 cycles, and had ANC blood draws on Day (D) 1, 2,6,7,8,9,10,15 in C1 (Covance Central Laboratory). Plin was given on D1, as a 30 min IV infusion, 30 min after Doc, and Peg, 24 hrs after Doc. Primary objective was to demonstrate non-inferiority (NI) of SA Plin vs SA Peg for duration of severe neutropenia (DSN) in C1. NI of Plin vs Peg would be declared if the upper limit of 95% confidence interval for the mean DSN difference between Plin and Peg would be <0.65 day. Other endpoints included C1 platelet count, C1 bone pain scores (validated questionnaire), C1-4 clinical sequelae of CIN through [febrile neutropenia (FN), infection, antibiotic and hospitalization rate, and Doc discontinuation (Discont) and delays], and safety (AEs, hematology and chemistry, vital signs) Results: Predefined DSN NI criterion between SA Plin and SA Peg was met. C1 Grade 4 toxicity was not different between Plin and Peg (p=NS). Clinical sequelae of CIN were comparable or slightly better for Plin vs Peg (see Table). Plin caused less bone pain (p=0.01) and less thrombocytopenia (p<0.0001 on D15) vs Peg. AE frequency and overall safety was comparable for SA Plin and SA Peg. Conclusions: SA Plin has efficacy for Doc CIN prevention non-inferior compared to SoC Peg, and accordingly has comparable (or numerically better) profile for clinical sequelae of CIN. Plin has an advantage for bone pain, platelet counts, convenience of use (same day vs next day dosing) over SoC Peg and has anticancer activity. Clinical trial information: NCT03102606