Background: Abemaciclib is a potent and selective inhibitor of CDK4 & 6 approved for treatment of HR+, HER2- metastatic breast cancer. In a Phase 1 study, abemaciclib showed activity in pts with advanced and/or metastatic NSCLC. This Phase 2 study evaluated the safety and efficacy of abemaciclib vs docetaxel in pts with Stage IV sqNSCLC previously treated with platinum-based chemotherapy. Methods: This multicenter, randomized, open-label trial, evaluated abemaciclib (200 mg PO every 12 hours daily) vs docetaxel (75 mg/m² IV on Day 1); both on 21 day cycle until disease progression. Adults with confirmed Stage IV NSCLC with measurable disease, ECOG PS ≤1, and who progressed during/after platinum-based chemotherapy were eligible. Pts were randomized 2:1 to receive abemaciclib or docetaxel. Primary endpoint was investigator-assessed PFS. Key secondary endpoints were ORR, DCR, OS, and safety. Results: 159 pts were randomized to abemaciclib (N = 106) and docetaxel (N = 53). Median age was 64 years. 84.3% pts were men. In ITT pts 125 PFS events were observed with median PFS of 2.5 m (95% CI: 1.7, 2.9) for abemaciclib and 4.2 m for docetaxel (95% CI: 2.8, 5.7; stratified HR: 1.77 [95% CI: 1.17, 2.67]; P = .0068). ORR was 2.8% (95% CI: 0.0, 6.0) for abemaciclib and 20.8% (95% CI: 9.8, 31.7) for docetaxel. The DCR (CR + PR + SD) was 50.9% (95% CI: 41.4, 60.5) for the abemaciclib treatment arm and 64.2% (95% CI: 51.2, 77.1) for the docetaxel treatment arm. Median OS was 7.0 m (95% CI: 5.0, 8.8) for abemaciclib and 12.4 m for docetaxel (95% CI: 7.1, 16.0; stratified HR: 1.33 [95% CI: 0.88, 2.02]; P = .1746). Exploratory biomarker data will be available at the meeting. The most common TEAEs with abemaciclib were anemia and diarrhea. Conclusions: In this Phase 2 study, single agent abemaciclib 200 mg did not improve the progression-free survival time over docetaxel; the instantaneous rate of disease progression/death at any given time point was higher with abemaciclib vs docetaxcel. No specific safety concerns were observed. Clinical trial information: NCT02450539