FDA granted Breakthrough Therapy Designation for the Janssen Pharmaceutical Companies of Johnson & Johnson’s JNJ-68284528 (JNJ-4528), an investigational B cell maturation antigen-directed chimeric antigen receptor T-cell therapy in previously treated patients with multiple myeloma.
The Breakthrough Therapy Designation is supported by data from the phase Ib/II CARTITUDE-1 study (NCT03548207), an open-label, multicenter clinical trial evaluating the safety and efficacy of JNJ-4528 in adults with relapsed or refractory multiple myeloma who have received at least three prior lines of therapy or are double refractory to a proteasome inhibitor and an immunomodulatory drug; have received a PI, IMiD and an anti-CD38 antibody; and who progressed on or within 12 months of their last line of therapy.
Currently active in the United States, the primary objective of the phase Ib portion of the study is to characterize the safety of JNJ-4528 and confirm the dose for future clinical trials. Phase II is evaluating efficacy with a primary endpoint of overall response rate, as defined by the International Myeloma Working Group response criteria, as well as duration of response and overall tolerability.
Initial data from the CARTITUDE-1 study were presented at the American Society of Hematology Annual Meeting.
The CARTITUDE-1 study design was informed by the phase I LEGEND-2 study (NCT03090659), the first-in-human study with LCAR-B38M CAR-T cells. In February 2019, FDA granted Janssen an Orphan Drug Designation for JNJ-4528. On April 3, 2019, Janssen announced the European Medicines Agency granted a PRIME designation for JNJ-4528 based on the CARTITUDE-1 and LEGEND-2 studies.
JNJ-4528, a structurally differentiated CAR-T with two BCMA-targeting single domain antibodies, identifies the investigational product being studied in the U.S. and Europe.
LCAR-B38M, which has the same CAR construct, identifies the investigational product in China. In December 2017, Janssen signed an agreement with Legend Biotech to jointly develop and commercialize LCAR-B38M in multiple myeloma. In China, the Phase II CARTIFAN-1 confirmatory trial (NCT03758417), sponsored by Nanjing Legend Biotech Co. Ltd. in collaboration with Janssen, is actively recruiting to further evaluate LCAR-B38M in patients with advanced relapsed or refractory multiple myeloma.
