Phase III study of ribociclib (LEE011) plus fulvestrant

Longtermsurvivor

Upcoming trial may be of interest to some bco members

Phase III study of ribociclib (LEE011) plus fulvestrant for the treatment of postmenopausal patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2–) advanced breast cancer (aBC) who have received no or only one line of prior endocrine treatment (ET): MONALEESA-3.

Sub-category:
ER+

Category:
Breast Cancer—HER2/ER

Meeting:
2016 ASCO Annual Meeting

Abstract No:
TPS624

Poster Board Number:
Poster Session (Board #106b)

Citation:
J Clin Oncol 34, 2016 (suppl; abstr TPS624)

Author(s): Peter A. Fasching, Guy Heinrich Maria Jerusalem, Xavier Pivot, Miguel Martin, Michele De Laurentiis, Kimberly L. Blackwell, Francisco J. Esteva, Stephen K. L. Chia, Caroline Germa, Zhongwen Tang, Shyeilla V. Dhuria, Dennis J. Slamon; Universitatsklinikum Erlangen, Erlangen, Germany; Centre Hospitalier Universitaire du Sart Tilman Liège and Liège University, Liège, Belgium; CHRU Besançon – IRFC, Besançon, France; Hospital General Universitario Gregorio Marañon, Madrid, Spain; National Cancer Institute "Fondazione Pascale", Naples, Italy; Duke University Medical Center, Durham, NC; Laura and Isaac Perlmutter Cancer Center, NYU Langone Medical Center, New York, NY; BC Cancer Agency, Vancouver, BC, Canada; Novartis Pharmaceuticals Corporation, East Hanover, NJ; University of California Los Angeles Medical Center, Santa Monica, CA

Abstract Disclosures

Abstract:

Background: Inhibition of the cyclin D–cyclin dependent kinase (CDK)4/6–retinoblastoma pathway may overcome ET resistance and enhance the efficacy of existing ET regimens in HR+, HER2– aBC. Combination of the CDK4/6 inhibitor ribociclib (LEE) with fulvestrant (FUL) has demonstrated potent tumor regressions in preclinical HR+ breast cancer (BC) models (O'Brien et al. Cancer Res 2014;74:Abstr 4756).

Methods: In this phase III, double-blind study (NCT02422615), postmenopausal patients with HR+, HER2– aBC (N≈660) will be randomized 2:1 to oral LEE (600 mg QD on Days 1–21 of each 28-day cycle) + FUL (500 mg intramuscularly on Days 1 and 15 of Cycle 1 and Day 1 of each cycle thereafter; Arm A) or placebo + FUL (Arm . Randomization is stratified by presence of lung or liver metastases and prior ET. Patients may have newly diagnosed aBC that is treatment-naïve, relapsed BC that has progressed at any time during/after (neo)adjuvant ET with no treatment for metastatic disease, relapsed BC that has progressed > 12 months after adjuvant ET and then subsequently progressed after 1 line of ET for metastatic disease, or newly diagnosed aBC that has progressed after 1 line of ET. Patients must have measurable disease or ≥ 1 predominantly lytic bone lesion, and an Eastern Cooperative Oncology Group performance status (ECOG PS) of ≤ 1. Prior chemotherapy (except for [neo]adjuvant chemotherapy), FUL, or any CDK4/6 inhibitor is prohibited. Tumor assessments occur every 8 weeks for the first 18 months and every 12 weeks thereafter until disease progression or study discontinuation. The primary endpoint is progression-free survival (PFS; local, RECIST v1.1). Secondary endpoints include overall survival, PFS (central, RECIST 1.1), overall response rate, clinical benefit rate, time to response, duration of response, safety and tolerability, time to deterioration of ECOG PS, patient-reported outcomes, and pharmacokinetics. Exploratory endpoints include molecular alterations in tumor biopsy and circulating tumor DNA. Clinical trial information: NCT02422615