Background: NAPA is an oral investigational agent, hypothesized to inhibit cancer stemness pathways, including STAT3 pathway implicated in cancer stem-cell viability. Synergistic antitumor activity of NAPA + PTX was observed in preclinical and early clinical testing. Methods: BRIGHTER is a randomized, double-blind, placebo-controlled phase 3 trial (NCT02178956), assessing efficacy and safety of NAPA + PTX versus PBO + PTX in pts with pretreated, advanced gastric and GEJ adenocarcinoma. The primary endpoint is overall survival (OS). Secondary endpoints include progression-free survival (PFS), objective response (ORR) and disease control (DCR) rates, and safety. Pts were randomized 1:1 to NAPA (960 mg total daily dose) + weekly PTX (80 mg/m²) or PBO + weekly PTX (80 mg/m²). Results: 714 pts were randomized from October 2, 2014, to December 12, 2016. At interim analysis of 380 events, the data safety monitoring board recommended trial unblinding when meeting the primary endpoint at final analyses appeared unlikely, though no safety concerns of clinical significance were identified. OS follow-up continued with median follow-up of 6.8 m (0.10-32.4) with final analysis performed at 565 events: 36.7%/63.2% (ECOG 0/1), 72.1%/27.9% (M/F), 74.6%/25.4% (gastric/GEJ). The mOS was 6.93 m vs 7.36 m in NAPA and PBO arms (HR 1.01 [95% CI, 0.86-1.20] p=0.8596), respectively. The mPFS was 3.55 m vs 3.65 m in NAPA and PBO arms (HR 1.00 [95% CI, 0.84-1.17] p= 0.9679), respectively. Among evaluable pts, DCR was 55 % vs 58% in NAPA and PBO arms Diff -3% (95% CI, -11%-5%, p= 0.6555), respectively, with an ORR of 16% vs 18% in NAPA and PBO arms Diff -2% (95% CI, -8%-4%, p=0.7358), respectively. The overall incidence of adverse events (AEs) was 98.6% vs 96.6% in NAPA and PBO arms without any additive toxicity. AEs ≥ Grade 3 occurred in 69.2% vs 59.7% in NAPA and PBO arms, with ≥Grade 3 diarrhea in 16.0% vs 1.4%, respectively. Conclusions: An international, placebo controlled phase 3 2^nd line study of NAPA + PTX did not improve OS or PFS in pts with gastric and GEJ adenocarcinoma. Addition of NAPA to PTX was tolerable. Clinical trial information: NCT02178956