Legend Biotech seeks to prioritize other product candidates in its pipeline.
Legend Biotech has terminated its phase 1 clinical trial for LB1901, an investigational autologous anti-CD4+ chimeric antigen receptor T-cell (CAR-T) therapy for the treatment of adults with relapsed/refractory T-cell lymphoma, according to an SEC filing.1
The termination was partially based on the lack of clinical benefit seen in an investigator-initiated study conducted in China on a similar Legend Biotech CAR-T product candidate which expresses the same CAR protein as LB1901. In addition, the SEC filing indicates that Legend Biotech made the termination in order to prioritize other product candidates in its pipeline.
The termination comes just 6 weeks after an FDA clinical hold on the trial was lifted on May 25, 2022.2 The hold had originally been placed on February 11, 2022, and came after Legend Biotech had paused the clinical trial and notified the FDA regarding a case of low CD4+ T-cell counts in the peripheral blood of the only patient who had been dosed at that time.3 According to a Legend Biotech press release from February 2022, the patient had not experienced drug-related serious adverse events and was being monitored in accordance with protocol.
The now-terminated clinical trial (NCT04712864) was an open-label, multicenter, first-in-human study. It had aimed to enroll 50 participants aged 18 years or older with histologically confirmed CD4+ r/r peripheral T-cell lymphoma (PTCL) or r/r cutaneous T-cell lymphoma who had previously been treated with at least two 2 prior lines of systemic antineoplastic therapy.
Participants were required to have an identified hematopoietic stem cell transplant donor available prior to enrollment and to have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Patients who had been previously treated with cellular immunotherapy or gene therapy products directed at any target, as well as patients who had had an allogeneic haematopoietic stem cells transplant, were excluded from the study.
The anti-CD4 CAR T cells were to be transduced with a lentiviral vector to express CD4 chimeric receptor domain. The primary end points for the study were to determine the recommended dose for expansion (RDE) and to then determine the recommended phase 2 dose (RP2D). Secondary end points included overall response, time to response, duration of response, disease control rate, progression-free survival, and overall survival.
Legend Biotech continues to go forward with clinical trials for other anti-cancer CAR-T therapies, including CARTITUDE-1 (NCT03548207), an ongoing phase 1b/2, open-label, single arm trial evaluating cilta-cel for the treatment of adult patients with r/r multiple myeloma, which is being carried out in collaboration with Janssen Biotech. Legend Biotech also recently announced FDA clearance of its IND application for LB1908, an investigational CAR-T therapy for the treatment of r/r gastric, esophageal, and pancreatic cancers.4