The U.S. Food and Drug Administration (FDA) has accepted and granted priority review of a supplemental new drug application for crizotinib, for use in pediatric patients with anaplastic lymphoma kinase (ALK)-positive, relapsed or refractory (R/R) systemic anaplastic large cell lymphoma (ALCL) .The Prescription Drug User Fee Act (PDUFA) decision date has been set for January 2021.
Crizotinib, a small molecule inhibitor of ALK, is currently indicated for the treatment of patients with ALK-positive or c-ros oncogene 1 (ROS1)-positive metastatic non-small cell lung cancer (NSCLC). The FDA previously granted crizotinib a breakthrough therapy designation for ALK-positive ALCL in May 2018, and the European Medicines Agency (EMA) agreed a pediatric investigation plan for crizotinib for the same indication in December 2019.
The FDA submission is based on results from two studies which showed compelling anti-tumor activity in patients receiving crizotinib, including children with R/R AKL-positive ALCL. The first study, ADVL0912 ( NCT00939770), is a phase I/II trial conducted in collaboration with the Children’s Oncology Group (COG) and the National Cancer Institute (NCI), evaluating tolerability and clinical activity of crizotinib in pediatric patients with ALK-positive R/R solid tumors or ALCL. The second study, A8081013 ( NCT01121588), is a phase Ib trial evaluating crizotinib activity in children and adults with ALK-positive tumors other than NSCLC, including those with R/R ALCL.
Despite high survival rates, many children with ALK-positive ALCL relapse. If approved, crizotinib would provide the first biomarker-driven treatment option for pediatric ALK-positive ALCL, marking a significant step towards targeted therapies for these patients.