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. 2022 May 30;40(5):1051–1065. doi: 10.1007/s10637-022-01253-3

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© The Author(s) 2022

Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 2 — Plasma pharmacokinetics of AMG 232, trametinib, and dabrafenib at steady-state for combinations of AMG 232 with trametinib and dabrafenib (Arm 1) or trametinib (Arm 2) given orally in adult subjects with MM. In Arms 1 and 2, AMG 232 was administered QD on days 1–7 of each cycle with a 14-day treatment-free period on days 8–21. In addition, trametinib was dosed continuously QD starting on day 8 of cycle 1. In Arm 1 only, dabrafenib was dosed continuously BID starting on day 8 of cycle 1. A. Mean (+SD) plasma concentration-time profiles of AMG 232 following AMG 232 dosing on cycle 1, day 7, when administered alone or on cycle 2, day 7, when co-administered with trametinib and dabrafenib [Arm 1] or trametinib [Arm 2]. B. Mean (+SD) plasma concentration-time profiles of trametinib following dosing of trametinib and dabrafenib [Arm 1] or trametinib alone [Arm 2] on cycle 1, day 21, without co-administration of AMG 232 (at the end of the 14-day AMG 232 treatment-free period) or on cycle 2, day 7, when co-administered with AMG 232. C. Mean (+SD) plasma concentration-time profiles of dabrafenib following dosing of dabrafenib and trametinib in Arm 1 on cycle 1, day 21, without co-administration of AMG 232 (at the end of the 14-day AMG 232 treatment-free period) or on cycle 2, day 7, when co-administered with AMG 232. Abbreviations: BID, twice a day; Chrt, cohort; D, dabrafenib; QD, once daily; SD, standard deviation; T, trametinib