Abstract OT2-02-08: A phase 2 randomized, double-blind, placebo-controlled study of ribociclib or placebo in combination with endocrine therapy for the treatment of premenopausal and postmenopausal Chinese women with HR+, HER2−, advanced breast cancer
Authors: Shao Zhimin , Zu Binghe , Tong Zhongsheng , Liu Qiang , Li Wei , Cai Li , Shen Kunwei , Zhao Wenhe , Yang Jin , Wang Chuan , Tang Woody , Sun Tingting , Han Yu , Gao Ruina 
Published: March 2020

Abstract
Background: Ribociclib (RIB) is a cyclin-dependent kinase 4/6 (CDK4/6) inhibitor that has demonstrated efficacy and safety in combination with endocrine therapy (ET) for the treatment of advanced breast cancer (ABC), but to date no studies have specifically evaluated RIB in a population in mainland China. This study aims to assess the efficacy and safety of RIB or placebo in combination with ET in premenopausal and postmenopausal Chinese patients with hormone receptor-positive (HR+), human epidermal growth factor receptor-2–negative (HER2−) ABC. It is also designed to investigate the pharmacokinetics (PK) of RIB in combination with ET.
Methods: In this phase 2 randomized, double-blind, placebo-controlled study, Chinese women with ABC will be included in a premenopausal or postmenopausal cohort (~150 patients each) and randomized 1:1 in each cohort to receive RIB or placebo. A further ~15 patients will be included in an open-label PK cohort. All patients must have HR+, HER2− ABC based on the most recently analyzed biopsy, with advanced disease not amenable to curative therapy. Patients must have measurable disease per Response Evaluation Criteria in Solid Tumors (version 1.1) or at least 1 predominantly lytic bone lesion, and Eastern Cooperative Oncology Group performance status score (ECOG PS) &lt; 2. Patients in the premenopausal cohort must be adult women who received no prior hormonal therapy and ≤ 1 line of chemotherapy (CT) for ABC and are eligible for ET. Patients in the postmenopausal and PK cohorts must be postmenopausal women who received no prior therapy (ET or CT) for ABC and are eligible for ET; patients who have received (neo)adjuvant therapy are eligible - if the prior neo(adjuvant) therapy included letrozole or anastrozole, the disease-free interval must be &gt; 12 months from the completion of treatment until randomization. Exclusion criteria include previous CDK4/6 inhibitor therapy; symptomatic visceral disease or any disease burden rendering patients ineligible for ET; central nervous system metastases; known human immunodeficiency virus infection history; and clinically significant uncontrolled heart disease. Patients in the premenopausal cohort will be randomized to 600 mg RIB oral (3 weeks on/1 week off) or placebo, in combination with a nonsteroidal aromatase inhibitor (2.5 mg letrozole [LET] oral or 1 mg anastrozole oral, chosen by investigator) and 3.6 mg goserelin subcutaneous. Patients in the postmenopausal cohort will receive RIB or placebo in combination with LET; those in the single-arm PK cohort will receive RIB in combination with LET. The primary endpoint of the premenopausal and postmenopausal cohorts is progression-free survival. Secondary endpoints are overall survival, overall response rate, clinical benefit rate, time to response, duration of response, and time to deterioration in ECOG PS. The objectives for the PK cohort are to characterize PK parameters of the RIB + LET combination, and of the RIB metabolites.
Citation Format: Zhimin Shao, Binghe Zu, Zhongsheng Tong, Qiang Liu, Wei Li, Li Cai, Kunwei Shen, Wenhe Zhao, Jin Yang, Chuan Wang, Woody Tang, Tingting Sun, Yu Han, Ruina Gao. A phase 2 randomized, double-blind, placebo-controlled study of ribociclib or placebo in combination with endocrine therapy for the treatment of premenopausal and postmenopausal Chinese women with HR+, HER2−, advanced breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr OT2-02-08.