Lorlatinib with or without chemotherapy in ALK-driven refractory/relapsed neuroblastoma: phase 1 trial results
| العنوان: | Lorlatinib with or without chemotherapy in ALK-driven refractory/relapsed neuroblastoma: phase 1 trial results |
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| المؤلفون: | Kelly C. Goldsmith, Julie R. Park, Kimberly Kayser, Jemily Malvar, Yueh-Yun Chi, Susan G. Groshen, Judith G. Villablanca, Kateryna Krytska, Lillian M. Lai, Patricia T. Acharya, Fariba Goodarzian, Bruce Pawel, Hiroyuki Shimada, Susan Ghazarian, Lisa States, Lynley Marshall, Louis Chesler, Meaghan Granger, Ami V. Desai, Rajen Mody, Daniel A. Morgenstern, Suzanne Shusterman, Margaret E. Macy, Navin Pinto, Gudrun Schleiermacher, Kieuhoa Vo, Holger C. Thurm, Joseph Chen, Marlon Liyanage, Gerson Peltz, Katherine K. Matthay, Esther R. Berko, John M. Maris, Araz Marachelian, Yael P. Mossé |
| المصدر: | Nature Medicine. 29:1092-1102 |
| بيانات النشر: | Springer Science and Business Media LLC, 2023. |
| سنة النشر: | 2023 |
| مصطلحات موضوعية: | General Medicine, General Biochemistry, Genetics and Molecular Biology |
| الوصف: | Neuroblastomas harbor ALK aberrations clinically resistant to crizotinib yet sensitive pre-clinically to the third-generation ALK inhibitor lorlatinib. We conducted a first-in-child study evaluating lorlatinib with and without chemotherapy in children and adults with relapsed or refractory ALK-driven neuroblastoma. The trial is ongoing, and we report here on three cohorts that have met pre-specified primary endpoints: lorlatinib as a single agent in children (12 months to 123I-metaiodobenzylguanidine (MIBG) response. Lorlatinib was evaluated at 45–115 mg/m2/dose in children and 100–150 mg in adults. Common adverse events (AEs) were hypertriglyceridemia (90%), hypercholesterolemia (79%) and weight gain (87%). Neurobehavioral AEs occurred mainly in adults and resolved with dose hold/reduction. The RP2D of lorlatinib with and without chemotherapy in children was 115 mg/m2. The single-agent adult RP2D was 150 mg. The single-agent response rate (complete/partial/minor) for NCT03107988. |
| تدمد: | 1546-170X 1078-8956 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_________::05cb1069b5caae85576f8251b56aaa50 https://doi.org/10.1038/s41591-023-02297-5 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi...........05cb1069b5caae85576f8251b56aaa50 |
| قاعدة البيانات: | OpenAIRE |
Find this article in full text from Springer Verlag. | تدمد: | 1546170X 10788956 |
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