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+
|ribociclib + exemestane|
|everolimus + exemestane|
|Phase 1b/2 (NCT02088684)||Any line, locally advanced or metastatic breast cancer, postmenopausal||ribociclib + BKM120 + fulvestrant||ER+
|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+
|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+
|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+
|ribociclib 600 mg + 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+
|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|
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