The Food and Drug Administration (FDA) has accepted for Priority Review the Biologics License Application (BLA) for loncastuximab tesirine (ADC Therapeutics) for the treatment of relapsed or refractory diffuse large B-cell lymphoma (DLBCL).
Loncastuximab tesirine (Lonca, formerly known as ADCT-402) is an antibody drug conjugate (ADC) composed of a humanized monoclonal antibody directed against human CD19 and conjugated through a linker to a pyrrolobenzodiazepine (PBD) dimer cytotoxin. Upon binding to a CD19-expressing cell, Lonca is internalized in the cell where enzymes release the cytotoxic PBD-based dimer, which binds to DNA to create interstrand cross-links. These cross-links are designed to disrupt DNA metabolic processes such as replication, which ultimately leads to cell death.
The BLA is supported by data from an open-label, single-arm phase 2 trial (LOTIS 2) that evaluated the efficacy and safety of Lonca in 145 adults with relapsed or refractory DLBCL following 2 or more lines of prior therapy; the primary end point was overall response rate.
Results of the study showed an overall response rate of 48.3% (n=70) and a complete response rate of 24.1% (n=35). As for safety, the most common grade 3 or greater treatment-emergent adverse events that occurred in at least 10% of patients were neutropenia (25.5%) with low incidence of febrile neutropenia (3.4%), thrombocytopenia (17.9%), increased gamma-glutamyl transferase (16.6%), and anemia (10.3%).
Additional data from subgroup analyses of LOTIS 2 will be presented at the upcoming 62nd American Society for Hematology (ASH) Annual Meeting on December 5, 2020.
A Prescription Drug User Fee Act (PDUFA) target date of May 21, 2021 has been set for this application.
For more information visit adctherapeutics.com.
ADC Therapeutics announces FDA accepts Biologics License Application and grants Priority Review for loncastuximab tesirine for treatment of relapsed or refractory diffuse large B-cell lymphoma. [press release]. Lausanne, Switzerland: ADC Therapeutics; November 20, 2020.