4549 Background: Baseline NER has been reported to be associated with outcomes of immuno-oncology based combination treatment in advanced renal cell carcinoma (aRCC). We report outcomes by baseline NER of patients with aRCC in the JAVELIN Renal 101 trial who received avelumab + axitinib (A + Ax) or sunitinib (S). Methods: We calculated the median NER (mNER) for patients in the A + Ax and the S arms at the data cutoff (April 20, 2020) for the 3rd interim analysis (IA3). Progression-free survival (PFS), overall survival (OS), and objective response (OR) by NER are reported. Multivariate Cox regression analyses of PFS and OS were also conducted. Results: At the IA3 cutoff date, the mNERs for the A + Ax arm (n = 383) and S arm (n = 396) were 29.2 and 27.0, respectively. OR, PFS and OS for both arms are summarized in the table below. Better observed treatment outcomes in OR (63.9% vs 55.2%) and median PFS (15.5 vs, 11.1 months) were observed for patients with a NER < median vs. NER ≥ median in the A + Ax arm, while there were not major differences in outcome based on NER in the S arm. The stratified hazard ratio (HR) for PFS in patients with a NER < median compared with those with a NER ≥ median in the A + Ax arm was 0.81 (95% CI, 0.630-1.035) and 0.93 (95% CI, 0.728-1.181) in the S arm. Patients with a NER < median had improved OS compared with those with a NER ≥ median in the A + Ax arm (stratified HR, 0.67; 95% CI, 0.481-0.940) and the S arm (stratified HR, 0.57; 95% CI, 0.424-0.779). Multivariate analysis showed that a low NER was associated with longer PFS and OS by treating baseline NER as either a continuous variable or a binary variable (dichotomized by median). Conclusions: Baseline NER may be predictive of OR and PFS in aRCC patients treated with A + Ax, and prognostic for overall survival regardless of therapy. Clinical trial information: NCT02684006. [Table: see text]