Ribociclib in Breast Cancer

Target Development Name Generic Name Trade Name Status
CDK4/6 LEE011 ribociclib   Trials completed with resultsa

a In a phase 1 study, an ER-positive breast cancer patient demonstrated a partial response when treated with single-agent ribociclib, one of two partial responses in a 70-patient cohort. The most common toxicities reported were neutropenia, leukopenia, nausea, and fatigue (Infante et al. 2014). In preliminary results from a phase 1b study, six patients with ER-positive, HER2-negative locally advanced or metastatic breast cancer were treated with ribociclib in combination with letrozole with one dose-limiting toxicity (neutropenia) reported. A 67% clinical benefit rate was reported in six patients (Table 1; Munster et al. 2014a, 2014b).

Table 1. Reported Trials with Ribociclib in Breast Cancer.

Reference Study Type / Phase Therapeutic setting Treatment Agent Mutation Status / Group # Pts in Study RR PFS (months) OS (months)
Munster et al. 2014a, 2014b (NCT01872260) Phase 1b 1st line
metastatic breast cancer
ribociclib + letrozole ER+ / HER2– 6 67%    

NOTE: CR = complete response; ER = estrogen receptor; OS = overall survival; PFS = progression-free survival; PR = partial response; Pts = patients; RR = response rate (CR + PR).

Table 2. Ongoing Clinical Investigation with Ribociclib in Breast Cancer.

Study Type / Phase / ID Therapeutic setting Prior therapy requirement Treatment Agent Mutation Status/Group # Patients in Study Study Start Date
Phase 2 (SIGNATURE, NCT02187783) 2nd line or greater, any cancer except non-triple negative breast cancer   ribociclib CDK4/6, cyclin D1/3, or p16 aberrations 90 August 2014
Phase 1b/2 (NCT01857193) 1st or greater, locally advanced or metastatic breast cancer, postmenopausal Recurrence during or within 12 months of adjuvant letrozole or anastrozole, or during or within 1 month of letrozole or anastrozole for metastatic disease ribociclib + everolimus + exemestane ER+
HER2–
185 September 2013
ribociclib + exemestane
everolimus + exemestane
Phase 1b/2 (NCT02088684) Any line, locally advanced or metastatic breast cancer, postmenopausal   ribociclib + BKM120 + fulvestrant ER+
HER2–
216 May 2014
ribociclib + BYL719 + fulvestrant
ribociclib + fulvestrant
Phase 1 (NCT02154776) 1st line, locally advanced or metastatic breast cancer; 2nd line or greater in the dose escalation phase   ribociclib + buparlisib + letrozole ER+
HER2–
50 June 2014
Phase 1b/2 (NCT01872260) 1st line, locally advanced or metastatic breast cancer, postmenopausal (phase 2, phase 1b dose expansions); Any line (Phase 1b dose escalation) No progression within 12 months of completing adjuvant letrozole ribociclib + letrozole ER+
HER2–
300 October 2013
BYL719 + letrozole
ribociclib + BYL719 + letrozole
Phase 2 (MONA LEESA-1, NCT01919229) 1st line, locally advanced or metastatic breast cancer, postmenopausal   ribociclib 400 mg + letrozole ER+ and/or PR+
HER2–
120 October 2013
ribociclib 600 mg + letrozole
letrozole
Phase 3 (MONA LEESA-2, NCT01958021) 1st line, locally advanced or metastatic breast cancer, postmenopausal No progression within 12 months of completing adjuvant letrozole or anastrole ribociclib + letrozole ER+ and/or PR+
HER2–
500 December 2013
placebo + letrozole
Phase 2 (SIGNATURE, NCT02187783) 2nd line or greater, any cancer, triple negative breast cancer   ribociclib CDK4/6, cyclin D1/3, or p16 aberrations 90 August 2014

NOTE: ER = estrogen receptor; HER2 = human epidermal growth factor receptor 2; PR = progesterone receptor.

Contributors: Justin M. Balko, Pharm. D., Ph.D., Ingrid A. Mayer, M.D., M.S.C.I., Mia Levy, M.D., Ph.D., Carlos L. Arteaga, M.D.

Suggested Citation: Balko, J., I. Mayer, M. Levy, C. Arteaga. 2015. Ribociclib in Breast Cancer. My Cancer Genome http://www.padiracinnovation.org/content/molecular-medicine/ribociclib-in-breast-cancer/ (Updated June 17).

Last Updated: July 22, 2015

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