LAUSR

AALL1931 (NCT04145531), a phase 2/3 study conducted in collaboration with the Children's Oncology Group, investigated the efficacy and safety of JZP458 (asparaginase erwinia chrysanthemi (recombinant)-rywn), a recombinant Erwinia asparaginase derived from a novel expression platform, in patients with acute lymphoblastic leukemia/lymphoblastic lymphoma who developed hypersensitivity/silent inactivation to E. coli-derived asparaginases. Each dose of a pegylated E. coli-derived asparaginase remaining in patients' treatment plan was substituted by six doses of intramuscular (IM) JZP458 on Monday/Wednesday/Friday (MWF). Three dosing regimens were evaluated: Cohort 1a, 25 mg/m2 MWF; Cohort 1b, 37.5 mg/m2 MWF; Cohort 1c, 25/25/50 mg/m2 MWF. The primary and key secondary efficacy outcomes were the proportion of patients maintaining adequate nadir serum asparaginase activity (NSAA ≥0.1 IU/mL) at 72 hours as well as at 48 hours during the first treatment course, respectively. 167 patients were enrolled: Cohort 1a (n=33), 1b (n=83), and 1c (n=51). Mean SAA levels (IU/mL) at 72-hr were 0.16 for Cohort 1a, 0.33 for Cohort 1b, and 0.47 for Cohort 1c; and 0.45, 0.88, and 0.66 at 48-hr, respectively. The proportion of patients achieving NSAA ≥0.1 IU/mL at 72-hr and 48-hr in Cohort 1c was 90% (44/49) and 96% (47/49), respectively. Simulated data from a population pharmacokinetic model matched the observed data well. Grade 3/4 treatment-related adverse events (TRAEs) occurred in 86/167 (51%) patients; TRAEs leading to discontinuation included pancreatitis (6%), allergic reactions (5%), increased alanine aminotransferase (1%), and hyperammonemia (1%). Study results demonstrate that IM JZP458 at 25/25/50 mg/m2 MWF is efficacious and has a safety profile consistent with those of other asparaginases.