https://www.selleckchem.com/products/selonsertib-gs-4997.html INTRODUCTION Cytotoxic agents have immunomodulatory effects, providing rationale for combining atezolizumab (anti-programmed death-ligand 1 [PD-L1]) with chemotherapy. The randomized phase III IMpower131 study (NCT02367794) evaluated atezolizumab with platinum-based chemotherapy in stage IV squamous non-small cell lung cancer (NSCLC). METHODS 1021 patients were randomized 111 to receive atezolizumab+carboplatin+paclitaxel (A+CP) (n=338), atezolizumab+carboplatin+nab-paclitaxel (A+CnP) (n=343), or carboplatin+nab-paclitaxel (CnP) (n=340) for four or six 21-day cycles; patients randomized to A+CP or A+CnP received atezolizumab maintenance therapy until progressive disease or loss of clinical benefit. Coprimary endpoints were investigator-assessed progression-free survival (PFS) and overall survival (OS) in the intention-to-treat (ITT) population. Secondary endpoints included PFS and OS in PD-L1 subgroups and safety. Primary PFS (January 22, 2018) and final OS (October 3, 2018) for A+CnP vs CnP are reported. RESULTS PFS improvement with A+CnP vs CnP was seen in the ITT population (median, 6.3 vs 5.6 months; hazard ratio [HR]=0.71, 95% CI 0.60-0.85; P=0.0001). Median OS in the ITT population was 14.2 and 13.5 months in the A+CnP and CnP arms, (HR=0.88, 95% CI 0.73-1.05; P=0.16), not reaching statistical significance. OS improvement with A+CnP vs CnP was observed in the PD-L1-high subgroup (HR=0.48, 95% CI 0.29-0.81), despite not being formally tested. Treatment-related grade 3-4 adverse events (AEs) and serious AEs occurred in 68.0% and 47.9% (A+CnP) and 57.5% and 28.7% (CnP) of patients. CONCLUSIONS Adding atezolizumab to platinum-based chemotherapy significantly improved PFS in patients with first-line squamous NSCLC; OS was similar between arms. (Funding F. Hoffmann-La Roche Ltd/Genentech, Inc.). BACKGROUND Sphingosine kinase (SphK) 1 has been reported as an important signaling node in anti-apoptotic signa