Background: With PD-1/PD-L1 inhibitors moving to first line in NSCLC, 2^nd/3^rd line NSCLC is a severe unmet medical need, dominated by docetaxel-based therapies with > 40% severe neutropenia and limited survival. Plin, a novel immune-enhancing small molecule, enhances dendritic cell maturation and T-Cell proliferation. In the ITT population, the Plin/Doc combination had superior Efficacy (mOS; HR = 0.82, p = 0.0399), Safety (lower Gr3/4 AE rate/pt/year (yr); p = 0.038) and better Quality of Life (QTWiST; p = 0.026) versus (vs) standard of care (SoC) Doc alone in advanced and metastatic NSCLC pts in DUBLIN-3 (Han, ESMO 2021) who failed platinum therapy. Here we report on the N-Sq pts subgroup. Methods: DUBLIN-3(NCT02504489) was a randomized, single-blind (pts only), active controlled Ph3 study in 2^nd/3^rd line stage IIIB/IV, EGFR wt NSCLC pts with a measurable lesion (RECIST 1.1) in the lung, and ECOG ≤ 2, conducted in US, Australia and China. Pts (n = 559) were randomized 1:1 to Plin/Doc or Doc/Placebo (21-day (D) cycle (C)). Doc (75 mg/m² on D1 and Plin 30 mg/m² on D1 and D8 were given by IV infusion. A post-hoc analysis of median Overall Survival (mOS) and restricted mean survival time (RMST) from K-M curves, OS rate at 24,36 and 48 month (Mo), and grade 4 neutropenia (Gr4N) rates was performed for the N-Sq patients (n = 153 for Plin/doc and n = 178 for Doc). Results: Baseline characteristics were balanced between both groups. Primary and key secondary objectives in the ITT population were met (Han, ESMO 2021). Plin/Doc was well tolerated. Estimated Adverse Event Rate per Year [95% CI] was 1.43 [1.13,1.81] for Plin/Doc versus 2.77 [2.33,3.28] for Doc alone (p < 0.001). The median OS benefit is 2.6 months (p = 0.023). The table below summarizes the results for the N-Sq subgroup. Conclusions: The addition of Plin to Doc was superior to SoC Doc alone for efficacy and safety in the clinically relevant subgroup of non-squamous EGFR-wild type, 2^nd/3^rd line NSCLC pts. Clinical trial information: NCT02504489.