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. 2023 Apr 3;29(5):1092–1102. doi: 10.1038/s41591-023-02297-5

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© The Author(s) 2023

Open Access This 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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 2 — a, Lorlatinib AUC_tau at steady state (cycle 1, day 15) compared to adult NSCLC levels. Dots represent individual patient AUC_tau. Cohort A1 (<18 years), cohort A2 (>18 years) and cohort B2 (<18 years, lorlatinib in combination with topotecan/cyclophosphamide). b, Lorlatinib exposure at steady state summarized descriptively by cohort/dose. As shown, no differences in PK were observed for patients on B2 who received lorlatinib with chemotherapy. Although a patient on A1 with the highest C_max and steady-state exposure for lorlatinib was a 12-year-old on DL5 who had a CNS DLT, there were six patients on A1 with steady-state exposures 1–2× higher than the adult 200-mg dose with no DLTs observed. CV, coefficient of variation; QD, once a day.

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