Abstract OT2-01-07: A phase 2 study of abemaciclib plus pembrolizumab for patients with hormone receptor positive (HR+), HER2 negative (HER2-) metastatic breast cancer (MBC)
Authors: Rugo H , Tolaney S , Dickler M , Kabos P , Ho C-L , Wildiers H , Jerusalem G , Alés-Martínez JE , Hossain A , Johnston E , Gianni L 
Published: March 2017

Abstract
Background:
Abemaciclib is a small molecule inhibitor of both cyclin-dependent kinase (CDK) 4 and CDK6 administered orally twice daily on a continuous schedule. In I3Y-MC-JPBA, a phase I study, abemaciclib demonstrated acceptable safety, tolerability, and single-agent activity as monotherapy in different tumor types, including HR+ MBC (Patnaik A,et al. Cancer Discov 2016;6:1–14). In MONARCH 1, a phase 2 study, abemaciclib demonstrated a 19.7% objective response rate (ORR) with a median duration of response (DoR) of 8.6 months, median progression-free survival (PFS) of 6.0 months, and clinical benefit rate (CBR) of 42.4% in patients with HR+, HER2- MBC whose disease progressed on or after endocrine therapy and chemotherapy (Dickler, M. et al. American Society of Clinical Oncology (ASCO), abstract #510 (2016).). Pembrolizumab is a humanized monoclonal antibody against the programmed death receptor-1 (PD-1) protein that has shown preliminary efficacy in single-arm monotherapy trials in ER+/HER2- advanced breast cancer.
Trial design:
This open-label, phase 2 study will evaluate the safety and preliminary efficacy of abemaciclib 150 mg given orally every 12 hours on days 1-21 of a 21-day cycle in combination with intravenous pembrolizumab 200 mg on day 1 of a 21-day cycle in approximately 75 patients with stage IV non-small cell lung cancer or HR+, HER2- MBC (ClinicalTrials.gov NCT02779751). The study will include 3 disease-specific cohorts, each with approximately 25 patients. Only the HR+, HER2- MBC cohort will be presented here.
Eligibility criteria:
Eligible patients for the MBC cohort include women with confirmed HR+, HER2- MBC who have completed at least 1 but no more than 2 prior chemotherapy regimens in the metastatic setting; will provide tumor tissue prior to and after treatment (cycle 3, day 1); have measurable disease (RECIST v.1.1), adequate organ function, an ECOG performance status ≤1, and a life expectancy ≥12 weeks; are ≥18 yrs of age and able to swallow oral medications; and have not received treatment with any CDK 4 and 6 inhibitors or PD-1 or PD-L1 inhibitors.
Specific aims:
The primary objective is to characterize the safety profile of the combination of abemaciclib and pembrolizumab. Key secondary objectives include ORR, DoR, disease control rate (DCR), PFS, overall survival (OS), and characterization of pharmacokinetics.
Statistical methods:
The safety population includes patients who received at least one dose of study drug. ORR, DoR, DCR, and PFS analyses will be evaluated according to RECIST v.1.1 and irRECIST for disease progression. Time-to-event variables, such as DoR, PFS, and OS, will be estimated by Kaplan-Meier methodology. An interim analysis of safety and preliminary efficacy may occur for each cohort after all patients have completed (or discontinued from) approximately 24 weeks of treatment. The final analysis of OS will occur based on data collected for approximately 12 months after the last patient receives treatment.
Target accrual:
Approximately 75 patients are planned for the trial; 25 patients will comprise the MBC cohort.
Contact information: 1-877-CTLILLY (1-877-285-4559).
Citation Format: Rugo H, Tolaney S, Dickler M, Kabos P, Ho C-L, Wildiers H, Jerusalem G, Alés-Martínez JE, Hossain A, Johnston E, Gianni L. A phase 2 study of abemaciclib plus pembrolizumab for patients with hormone receptor positive (HR+), HER2 negative (HER2-) metastatic breast cancer (MBC) [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr OT2-01-07.