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
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 <18 years); lorlatinib as a single agent in adults (≥18 years); and lorlatinib in combination with topotecan/cyclophosphamide in children (<18 years)...
May 2023: Nature Medicine