Abstract OT2-01-08: Phase 2 study of abemaciclib plus tamoxifen or abemaciclib alone in women with previously treated hormone receptor-positive (HR+), HER2- metastatic breast cancer
Authors: Diéras V , Hamilton E , Johnston EL , Forrester T , Martín M 
Published: March 2017

Abstract
Background:
Abemaciclib, an oral drug administered twice daily on a continuous schedule, is a specific inhibitor of both CDK4 and CDK6. In MONARCH 1, abemaciclib demonstrated evidence of single-agent activity and an acceptable safety profile in patients with heavily pretreated HR+, HER2- metastatic breast cancer (MBC) whose disease progressed on or after endocrine therapy and chemotherapy; with a confirmed objective response rate of 19.7% and a median duration of response of 8.6 months (Dickler, M. et al. American Society of Clinical Oncology (ASCO), abstr #510 (2016)). This Phase 2 study I3Y-MC-JPCG will evaluate the potential to enhance the risk/benefit profile of abemaciclib in women with previously treated HR+, HER2- MBC, either administered in combination with endocrine therapy or as monotherapy (at the maximum recommended single-agent dose with primary prophylactic antidiarrheal medication or at a lower dose of abemaciclib monotherapy). Such intervention with prophylactic loperamide may increase dose intensity and further optimize the clinical benefit for patients.
Trial design:
Study JPCG (NCT02747004) is a Phase 2 multicenter, randomized, open-label trial with 3 separate treatment arms in patients with HR+, HER2- MBC who have progressed on or after prior endocrine therapy and have received prior treatment with chemotherapy. Patients will be stratified based on presence of liver metastases and prior use of tamoxifen in the advanced/metastatic setting and will be randomized in a 1:1:1 ratio to receive abemaciclib 150 mg Q12H plus tamoxifen 20 mg every day (Arm A) or abemaciclib 150 mg Q12H monotherapy (Arm B); or abemaciclib 200 mg Q12H monotherapy plus primary prophylactic loperamide (Arm C).
Eligibility criteria:
Eligible patients include women with HR+, HER2- MBC with evidence of relapse or disease progression following endocrine therapy who have received prior treatment with at least 2 chemotherapy regimens, of which at least 1 but not more than 2 regimens have been administered in the metastatic setting. Patients are required to have measurable disease, adequate organ function, an ECOG PS of ≤1, and no prior treatment with any CDK4 and CDK6 inhibitor.
Specific aims:
The primary objective of JPCG is to evaluate the progression-free survival per RECIST v1.1, of abemaciclib 150 mg Q12H plus tamoxifen 20 mg QD, abemaciclib 150 mg Q12H monotherapy, and abemaciclib 200 mg Q12H plus prophylactic loperamide in women with HR+, HER2- MBC who have progressed on or after prior endocrine therapy and received prior chemotherapy. Secondary objectives are to evaluate response rates, overall survival, safety, pharmacokinetics, and quality of life. Exploratory objectives include evaluation of the associations between biomarkers relevant to abemaciclib and clinical outcomes.
Statistical methods:
Assuming a hazard ratio of 0.667, the study yields approximately 80% statistical power to detect superiority of Arm A over Arm C at a 1-sided alpha level of 0.10 using a log-rank test. Arms B and C will be compared using an informal non-inferiority rule.
Target accrual:
Approximately 225 patients.
Contact information:
For further information, please contact 1-877-CTLILLY (1-877-285-4559).
Citation Format: Diéras V, Hamilton E, Johnston EL, Forrester T, Martín M. Phase 2 study of abemaciclib plus tamoxifen or abemaciclib alone in women with previously treated hormone receptor-positive (HR+), HER2- metastatic breast cancer [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 OT2-01-08.