Phase 1b/2 trial of ribociclib plus binimetinib in metastatic NRAS-mutant melanoma: Safety, efficacy, and recommended phase 2 dose (RP2D).
Martin H Schuler, Paolo A Ascierto, Filip Yves Francine Leon de Vos, Michael Andrew Postow, Carla ML Van Herpen, Matteo S Carlin, Jeffrey A Sosman, Carola Berking, Georgina V Long, Amy Weise, Ralf Gutzmer, Martin Kaatz, Grant A McArthur, Gary Schwartz, Adil Daud, Kati Maharry, Padmaja Yerramilli-Rao, Lisa Zimmer, Viviana Bozon, Rodabe Navroze Amaria
JOURNAL OF CLINICAL ONCOLOGY | AMER SOC CLINICAL ONCOLOGY | Published : 2017
9519 Background: Simultaneous inhibition of MEK and CDK4/6 may suppress MAPK pathway activation and cell-cycle checkpoint dysregulation in NRAS-mutant melanoma, resulting in enhanced antitumor activity. Phase 1b data are reported. Methods: The phase 1b primary objective was to determine maximum tolerated dose (MTD)/RP2D. A 28-d cycle of oral ribociclib (RIBO) once daily (QD) for 21 d + oral binimetinib (BINI) twice daily (BID) for 28 d, and a 21-d cycle of RIBO QD + BINI BID, both for 14 d per cycle, were evaluated. Secondary objectives were to evaluate efficacy, safety and pharmacodynamics. Results: Based on dose escalation (van Herpen, ESMO 2015), MTD was 600mg RIBO/45mg BINI for the 21-d..View full abstract