Lyell Immunopharma's LYL314 Gains RMAT Status for Refractory Large B-Cell Lymphoma Treatment

Lyell Immunopharma, Inc., a clinical-stage company focused on advancing CAR T-cell therapies for cancer patients, has announced that its product LYL314 has been granted Regenerative Medicine Advanced Therapy (RMAT) designation by the U.S. Food and Drug Administration (FDA). This designation is aimed at treating adult patients with relapsed and/or refractory large B-cell lymphoma who have undergone at least two prior lines of therapy.

LYL314 is a next-generation CAR T-cell therapy that targets both CD19 and CD20 antigens, designed to improve complete response rates and extend the duration of response compared to existing CD19-targeted therapies for large B-cell lymphoma. The RMAT designation for LYL314 recognizes its potential to meet critical patient needs and allows for increased communication frequency with the FDA regarding its development.

The RMAT designation offers the benefits of both Fast Track and Breakthrough Therapy designations, facilitating early interactions with the FDA. These interactions can be pivotal in speeding up the development and review process for therapies that address serious or life-threatening conditions. The decision to grant RMAT status to LYL314 was based on promising clinical data from an ongoing Phase 1/2 trial.

The initial results of this trial were presented at the American Society for Hematology Annual Meeting in December 2024. The trial included 23 patients with relapsed or refractory large B-cell lymphoma in their third or subsequent line of treatment. Among the 17 patients evaluated for efficacy, a remarkable 94% exhibited an overall response, with 71% achieving a complete response within three months. After a median follow-up of 6.3 months, 71% of the patients continued to respond to the treatment.

The safety profile of LYL314 was also notable. Of the 23 patients evaluated for safety, none experienced Grade 3 or higher cytokine release syndrome. However, 13% reported Grade 3 immune effector cell-associated neurotoxicity syndrome, which resolved to Grade 2 or lower within five days with standard treatment.

Looking forward, Lyell plans to present additional clinical data from the Phase 1/2 trial during 2025. This includes more mature data for patients in the third or later line setting and initial results for those in the second line setting by mid-2025. Furthermore, Lyell aims to launch two pivotal programs: one for patients in the third or later line setting by mid-2025 and another for those in the second line setting by early 2026.

The RMAT designation is part of the 21st Century Cures Act, designed to expedite the development of regenerative medicine therapies for serious or life-threatening diseases. Eligible therapies must demonstrate the potential to address unmet medical needs, supported by preliminary clinical evidence.

LYL314, in addition to its RMAT designation, has also received Fast Track Designation from the FDA. Lyell Immunopharma is committed to advancing its pipeline of next-generation CAR T-cell therapies to provide durable and effective treatments for patients with both hematologic malignancies and solid tumors. The company's innovative approach focuses on enhancing CAR T-cell attributes to overcome challenges like tumor microenvironment resistance and ensure sustained anti-tumor activity.