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.mycancergenome.org/content/molecular-medicine/ribociclib-in-breast-cancer/ (Updated June 17).
Last Updated: July 22, 2015