FDA Places Clinical Hold on Phase 1 Trial Examining CAR T-cell Therapy LB1901 in T-cell Lymphoma

US FDA

The FDA has placed a clinical hold on a phase 1 trial (NCT04712864) evaluating the safety and efficacy of the autologous CAR T-cell product LB1901 as a potential therapeutic option in adult patients with relapsed or refractory T-cell lymphoma (TCL).¹

The trial was paused by Legend Biotech Corporation, the drug developer, after low CD4-positive T-cell counts were observed in the peripheral blood of the first and only patient to have been dosed with the investigational product to date. The global, clinical-stage biotechnology company then proceeded to notify the regulatory agency.

An official clinical hold letter from the FDA is expected by March 11, 2022, but the company shared that the patient has not experienced serious treatment-related toxicities and is being monitored in accordance with the trial protocol.

LB1901 was designed to target the surface membrane glycoprotein CD4, which is uniformly expressed in many subtypes of TCL.

The first-in-human, open-label, multicenter trial enrolled patients with a histologically confirmed diagnosis of CD4-positive peripheral T-cell lymphoma (PTCL), PTCL not otherwise specified (PTCL-NOS), angioimmunoblastic, or relapsed/refractory cutaneous T-cell lymphoma (CTCL).

Patients were required to be at least 18 years of age, have relapsed or refractory disease with at least 2 prior lines of systemic antineoplastic therapy received, an identified hematopoietic stem cell transplant donor available before enrollment, an ECOG performance status of 0 or 1, and acceptable organ function.²

Those with confirmed CD30-positive PTCL or mycosis fungoides must have previously received brentuximab vedotin (Adcetris). Patients also should have previously received at least 2 lines of standard-of-care therapies. Those with PTCL-NOS or AITL had to have at least 1 measurable lesion per International Myeloma Working Group response criteria, and those with CTCL needed to have stage IIB disease or higher.

If patients had histologically confirmed CD8-positive TCL, received prior CAR T-cell therapy or gene therapy or CD4-targeted therapy, had a history of allogeneic hematopoietic stem cell transplant, received select antitumor therapy before apheresis, an immunosuppressant, therapeutic anticoagulants, or they received central nervous system (CNS) disease prophylaxis, they were excluded.

Patients also could not have a history of hepatitis B or C infection, autoimmune disease requiring systemic immunosuppression, a primary immunodeficiency, active CNS associated with an underlying malignancy, impaired cardiac function, or clinically significant cardiac disease.

The primary outcome measures for the trial include characterizing the safety and tolerability of LB1901 and identifying the optimal dose or recommended expansion dose, and to further characterize the safety and tolerability of the product with that dose and determine the recommended phase 2 dose. Secondary outcome measures comprise overall response, time to response, duration of response, disease control rate, progression-free survival, and overall survival.

In December 2020, the FDA cleared the investigational new drug (IND) application to examine LB1901 in the treatment of this patient population.³ Under the IND, the company initiated the phase 1 trial to further examine the use of the product in these patients in the United States.

References

1. Legend Biotech announces FDA clinical hold of its phase 1 clinical trial for LB1901. News release. Legend Biotech Corporation; February 15, 2022. Accessed February 16, 2022. https://bwnews.pr/3gPz9o7
2. Study of CD4-targeted chimeric antigen receptor T-cells (CD4- CAR-T) in subjects with relapsed or refractory T-cell lymphoma. ClinicalTrials.gov. Updated February 16, 2022. Accessed February 16, 2022. https://clinicaltrials.gov/ct2/show/NCT04712864
3. Legend Biotech announces FDA clearance of IND for LB1901, an investigational autologous anti-CD4 CAR-T therapy for relapsed or refractory T-cell lymphoma. News release. Legend Biotech Corporation; December 14, 2020. Accessed February 16, 2022. https://bit.ly/3uZy0CK