Abstract OT1-03-04: A phase 2 study of abemaciclib in patients with brain metastases secondary to hormone receptor positive breast cancer
Authors: Anders C , Zielinski C , Klise SR , Wang HT , Thornton D , Tolaney SM 
Published: May 2016

Abstract
Background:
Abemaciclib, an oral drug administered twice daily on a continuous schedule, is an inhibitor of both CDK4 and CDK6. In study JPBA, abemaciclib demonstrated evidence of single-agent activity in a cohort of patients with heavily pretreated metastatic breast cancer (MBC, median of 7 prior therapies); all responses were observed in women with hormone receptor positive (HR+) disease. Preclinical results demonstrating that abemaciclib crosses the blood-brain barrier coupled with the clinical responses observed in study JPBA support further investigation of abemaciclib in the current phase 2 trial (JPBO) of patients with brain metastases secondary to HR+ breast cancer.
Trial design:
Study JPBO (NCT02308020) is an open-label, phase 2 trial that will evaluate the safety and efficacy of abemaciclib 200 mg administered orally every 12 hours in patients with HR+ MBC and brain metastases. The study will consist of 3 parts; 2 of these parts will each accrue from 23 to 56 patients.These 2 parts will include patients with HER2+ breast cancer (Part A) and HER2- breast cancer (Part B). Part C will include approximately 8 MBC patients with either HER2+ or HER2- disease who have 1 to 3 intracranial lesions and for whom surgical resection is clinically indicated, with the goal of assessing drug concentrations in plasma, CSF, and brain tumor tissue. These patients may resume abemaciclib post-operatively.
Eligibility criteria:
Eligible patients include women with HR+ MBC who have completed local therapy ≥14 days prior to abemaciclib treatment, a life expectancy ≥12 weeks, and a Karnofsky performance status of ≥70. Part A includes MBC with confirmed HER2 overexpression and/or amplification (HER2+) status. Part B includes MBC that does not demonstrate HER2 overexpression and/or amplification (HER2-). For Parts A and B, patients will have ≥1 new or not previously irradiated measurable metastatic brain lesion ≥10 mm in the longest diameter or a progressive previously irradiated metastatic brain lesion identified by gadolinium-enhanced MRI. For Part C (surgical), patients have either HER2+ or HER2- MBC with brain lesion(s) for which surgical resection is clinically indicated and agree to provide post-treatment brain tumor tissue.
Specific aims:
The primary efficacy measure is objective intracranial response rate (complete response + partial response) as defined by Response Assessment in Neuro-Oncology brain metastases response criteria. Secondary intracranial objectives include best overall response, duration of response, disease control rate, and clinical benefit rate. The following overall objectives (intracranial + extracranial) include: overall survival, objective response rate, and progression-free survival. Change in neurologic symptoms will also be assessed.
Statistical methods:
Two separate Simon 2-stage designs will be employed for Part A and Part B. Each design assumes a 1-sided type-I error of 0.05 and 80% power. All tests will be conducted at a 2-sided alpha level of 0.05, unless otherwise stated. All confidence intervals will be given at a 2-sided 95% level.
Target accrual:
Approximately 120 patients.
Contact information:
For further information, please contact 1-877-CTLILLY (1-877-285-4559).
Citation Format: Anders C, Zielinski C, Klise SR, Wang HT, Thornton D, Tolaney SM. A phase 2 study of abemaciclib in patients with brain metastases secondary to hormone receptor positive breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr OT1-03-04.