A phase II/III study of JZP-458 in patients with acute lymphoblastic leukemia (ALL)/lymphoblastic lymphoma (LBL) who are hypersensitive to E. coli-derived asparaginases.

Abstract

TPS7568 Background: L-asparaginase is an important component of ALL therapy and the inability to receive asparaginase secondary to hypersensitivity has been associated with poor patient (pt) outcomes. Alternative options for pts after hypersensitivity reactions are needed. JZP-458 is a recombinant Erwinia asparaginase produced using a novel Pseudomonas fluorescens expression platform that yields an enzyme with no immunologic cross-reactivity to E. coli–derived asparaginases. In a phase 1 study, JZP-458 was well tolerated and maintained adequate (≥0.1 IU/mL) serum asparaginase activity (SAA), a surrogate marker for asparagine depletion, for up to 72 hrs in healthy adults. Methods: This is a pivotal, open-label, multicenter, dose confirmation, and pharmacokinetic (PK) study (NCT04145531) of JZP-458 in pts with ALL/LBL who develop hypersensitivity reactions to a long-acting E. coli–derived asparaginase and have ≥1 course of asparaginase remaining in their treatment plan (Table); 6 doses of JZP-458 will be substituted for each remaining course. Treatment duration will depend on the number of asparaginase courses remaining in the treatment plan. The study has 2 sequential parts: Part A will determine the dose of intramuscular (IM) JZP-458 and confirm safety/efficacy; Part B will explore the dose/schedule of intravenous (IV) JZP-458. Blood samples will be collected to determine SAA levels and pts will be monitored for adverse events. Immunogenicity of JZP-458 will be assessed. Primary objectives are to determine (1) the efficacy of IM JZP-458 measured by the last 72-hr nadir SAA (NSAA) level (≥0.1 IU/mL) during the first treatment course, and (2) the safety/tolerability of IM JZP-458. Secondary objectives are to determine the efficacy (measured by the last 48-hr NSAA level [≥0.1 IU/mL] and the last 48- and 72-hr NSAA levels [≥0.4 IU/mL]), PK, and immunogenicity of IM JZP-458. Exploratory objectives include efficacy, safety, PK, and immunogenicity of IV JZP-458. The trial is active and enrolling. Clinical trial information: NCT04145531 . [Table: see text]