Background: Lung-MAP (S1400) is a National Clinical Trials Network “umbrella” trial for previously-treated SqNSCLC. Sub-study S1400B included patients (pts) with tumors harboring PI3K mutations.Taselisib (GDC-0032), a potent, small molecule inhibitor of Class 1 PI3K with beta isoform sparing selectivity, has been shown to be a potent inhibitor in preclinical models of PIK3CA-mutant tumors. Methods: Eligibility stipulated progressive SqNSCLC after primary platinum-based therapy and presence of a PIK3CA mutation as determined by Foundation Medicine (FMI+) NGS. . The primary analysis population was a subgroup of the total PIK3CA mutation group (GNE+) with alterations limited to substitutions: E542K, E545A, E545G, E545K, E545Q, H1047L, H1047R, H1047Y. Primary endpoint was response rate (RR) in GNE+ pts. The initial protocol randomized PIK3 mt (+) pts to taselisib 4 mg po daily or docetaxel, but was amended to single arm phase II trial of taselisib with interim analysis based on first 20 eligible GNE+ pts evaluable for response, stipulating closure for futility if < 2 responses were observed. Results: 26 eligible pts, 7% of those registered to S1400, received taselisib; of these , 21 (81%) were GNE+. Of the 20 eligible, response-evaluable GNE+ pts, one pt with PIK3CA E545K gene alteration responded (5% RR, 95% Confidence Interval [CI] 1%, 24%). 13 pts had stable disease. Median PFS was 2.5 mos (95% CI, 1.7-4.0 mos) and 2.7 mos (95% CI, 1.8-3.4 mos) among GNE+ and FMI+ pts, respectively. 26 FMI+ pts were evaluable for toxicity: two grade 5 events (cardiac arrest, respiratory failure), neither clearly attributable to treatment, were recorded, along with one instance each of grade 4 AEs (dyspnea, thrombocytopenia, pneumonitis). Grade 3 AEs included 5 pts each with hyperglycemia or diarrhea, and 3 with lymphopenia. Overall survival data is premature. Conclusions: Study S1400B failed to meet its primary endpoint and was closed December 2016 at interim analysis for futility. Toxicities were manageable. The trial is unique in cataloguing the diversity of mutations in the PI3K pathways in SqNSCLC Clinical trial information: NCT02785913