Background: Abemaciclib is a selective inhibitor of CDK4 & 6 approved to treat HR+, HER2- metastatic breast cancer (MBC) patients (pts) as monotherapy and in combination with fulvestrant. In preclinical models, abemaciclib administered with anti-programmed death-ligand 1 (PD-L1) antibody therapy synergistically induced anti-tumor response and immunologic memory. A Phase I study (JPBJ, NCT02079636) of abemaciclib plus pembrolizumab (Merck & Co.), a programmed death receptor 1 (PD-1) antibody, demonstrated stable disease in 65% of pts with stage IV NSCLC along with a generally manageable safety profile. Methods: JPCE is a multicenter, nonrandomized, open-label, Phase 1b study of abemaciclib plus pembrolizumab in pts with HR+, HER2- MBC or stage IV NSCLC. Key eligibility criteria for the MBC cohort were: HR+, HER2- MBC with 1 - 2 prior chemotherapy regimens, measurable disease, adequate organ function, ECOG PS ≤1, and no prior treatment with CDK4 & 6 or PD-1 & PD-L1 inhibitors. The primary objective was to assess safety of the combination per CTCAE v4.0. Secondary objectives were: objective response rate (ORR), progression-free survival, duration of response, disease control rate, overall survival, pharmacokinetics and pt-reported disease-related symptoms. Pts received the maximum tolerated dose established in JPBJ; orally administered abemaciclib 150 mg twice daily plus IV administered pembrolizumab 200 mg, day 1 of each 21-day cycle. Results: Twenty-eight pts were enrolled in the MBC cohort. Abemaciclib plus pembrolizumab demonstrated a generally manageable safety profile in pts with HR+, HER2- MBC. Single agent toxicity profiles reported previously were not exacerbated, and no new safety signals were detected. Initial ORR was 14.3%. Patient PD-L1 status by IHC staining (positive ≥1%; negative < 1%), efficacy, and safety data from the 24-week analysis will be presented. Conclusions: Abemaciclib plus pembrolizumab demonstrated a generally manageable safety profile upon initial review (Rugo et al. SABCS 2017). Assessment of the effectiveness of this novel combination, with reference to PD-L1 status, for the treatment of pts with HR+, HER2- MBC is ongoing. Clinical trial information: NCT02779751