Abstract P5-21-28: Phase Ib study of ribociclib + letrozole in Asian non-Japanese patients with hormone receptor-positive, HER2-negative advanced breast cancer: MONALEESASIA
Authors: Yap YS , Ito Y , Suarez-Vizcarra J , Liu X , Han Y , Germa C , Chiu J 
Published: February 2018

Abstract
Background: First-line ribociclib (RIB; a selective cyclin-dependent kinase 4/6 inhibitor) + letrozole (LET) significantly prolonged progression-free survival vs placebo + LET in patients (pts) with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2–) advanced breast cancer (ABC). The Phase Ib MONALEESASIA dose-escalation/-expansion study (NCT02333370) is investigating RIB + LET in Asian pts with HR+, HER2– ABC; here we report results in Asian non-Japanese pts.
Methods: Asian, non-Japanese postmenopausal women with HR+, HER2– ABC, with no prior systemic treatment for ABC, received RIB (starting dose 400 mg/day; 3-weeks-on/1-week-off; option to escalate or de-escalate) + LET (2.5 mg/day; continuous) until disease progression or discontinuation for other reasons. Dose escalation was guided by a Bayesian Logistic Regression Model (BLRM) with overdose control. The primary objective of the dose-escalation part was to estimate the maximum tolerated dose (MTD) and/or recommended Phase II dose (RP2D), based on the BLRM, safety data, and pharmacokinetic analyses; secondary/exploratory objectives included safety and tolerability, and antitumor activity.
Results: At data cut-off (January 16, 2017), 26 pts were enrolled; 13 in the dose escalation (RIB 400 mg: n=6; RIB 600 mg: n=7) and 13 in the 600 mg dose expansion. Treatment was ongoing in 18 pts (69%; 400 mg: n=3; 600 mg: n=15); the most common reason for discontinuation was disease progression (400 mg: n=3; 600 mg: n=4). One dose-limiting toxicity occurred at 600 mg (Grade 3 increased alanine transaminase [ALT]). The MTD/RP2D was declared as 600 mg/day RIB (3-weeks-on/1-week-off) + 2.5 mg/day LET (continuous). The most common all-grade, all-cause adverse events (AEs; ≥35% in either cohort; 400 mg vs 600 mg) were neutropenia (n=1 [17%] vs n=8 [40%]), increased ALT (n=1 [17%] vs n=7 [35%]), decreased neutrophil count (n=3 [50%] vs n=7 [35%]), and alopecia (n=3 [50%] vs n=2 [10%]). All-cause Grade 3/4 AEs occurred in 4 pts (67%) at 400 mg and 18 pts (90%) at 600 mg; the most common (≥25% in either cohort; 400 mg vs 600 mg) were decreased neutrophil count (n=3 [50%] vs n=7 [35%]) and neutropenia (n=1 [17%] vs n=6 [30%]). At least one RIB dose reduction due to AEs occurred in 2 pts at 400 mg and 10 pts at 600 mg. At least one RIB dose interruption due to AEs occurred in 4 pts at 400 mg and 13 pts at 600 mg. Post-baseline QTcF &gt;480 ms occurred in 0 pts at 400 mg and 4 pts (20%) at 600 mg. No pt had a post-baseline QTcF &gt;500 ms. The overall response rate was 50% (n=3) at 400 mg and 35% (n=7) at 600 mg (all partial responses). Stable disease was reported in 1 pt (17%) at 400 mg and 8 pts (40%) at 600 mg.
Conclusions: RIB + LET demonstrated a manageable safety profile with preliminary signs of antitumor activity in Asian non-Japanese pts with HR+, HER2– ABC; the safety profile was broadly consistent with that seen in non-Asian pts. The MTD/RP2D was declared as 600 mg/day RIB (3-weeks-on/1-week-off) + 2.5 mg/day LET (continuous). Further safety and efficacy data for RIB + LET will be reported in this pt population after the dose expansion is completed.
Citation Format: Yap YS, Ito Y, Suarez-Vizcarra J, Liu X, Han Y, Germa C, Chiu J. Phase Ib study of ribociclib + letrozole in Asian non-Japanese patients with hormone receptor-positive, HER2-negative advanced breast cancer: MONALEESASIA [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P5-21-28.