Background: Abemaciclib is an oral, selective inhibitor of CDK4 and CDK6 dosed on a continuous schedule. In a phase 1 trial, abemaciclib demonstrated single-agent activity in refractory HR+ metastatic breast cancer (MBC) with some tumor responses occurring after 8 or more mos of therapy. Methods: MONARCH 1 is a phase 2 single-arm study designed to evaluate safety and efficacy of abemaciclib monotherapy in women with HR+/HER2- MBC whose disease progressed on or after endocrine therapy and chemotherapy. Eligible pts had measurable disease, ECOG PS of 0/1, no CNS metastases, and received at least 1 but no more than 2 lines of chemotherapy in the metastatic setting. Abemaciclib (200 mg) is administered orally on a continuous schedule every 12 hours until disease progression. A sample size of approximately 128 pts was planned to evaluate the primary objective of investigator-assessed objective response rate (ORR) using RECIST v1.1, with interim and final analyses at 8 and 12 mos after the last pt started treatment, respectively. Results: A total of 132 pts have been treated with abemaciclib monotherapy. Pts had a median of 3 lines of prior therapy for advanced disease, including a median of 2 lines of chemotherapy for advanced disease. Median age was 58 (36-89), 44.7% of pts had PS 1, 90.2% had visceral disease, and 85.6% had ≥ 2 metastatic sites. At the 8 mo interim, 35.6% of pts had received ≥ 8 cycles of therapy; the confirmed ORR (per RECIST v1.1) was 17.4%, the clinical benefit rate (CR + PR + SD ≥ 6 mos) was 42.4%, and median PFS was 5.7 mos. Of the 22 pts who remained on treatment at the 8 mo interim, 13 had responded and 9 had SD. The 5 most common TEAEs were diarrhea, fatigue, nausea, decreased appetite, abdominal pain; discontinuations due to AEs were infrequent (6.8%). Conclusions: Abemaciclib induces objective tumor responses as a monotherapy in pts with refractory HR+ HER2- MBC following multiple prior therapies. Treatment was well tolerated, allowing prolonged exposure to therapy. Updated efficacy and tolerability data will be provided at the time of presentation. Clinical trial information: NCT02102490