Lyell Shares Positive Phase 1-2 IMPT-314 Trial Results for B-cell Lymphoma at 2024 ASH Meeting

In a recent announcement, Lyell Immunopharma, Inc., a clinical-stage company specializing in advanced CAR T-cell therapies, shared promising initial clinical data from its ongoing Phase 1-2 study of IMPT-314. This study targets patients with large B-cell lymphoma, specifically those who have relapsed or are refractory after receiving previous treatments. The data were presented at the 66th American Society of Hematology (ASH) Annual Meeting, highlighting the potential of IMPT-314 as a promising therapeutic option for this patient group.

IMPT-314 is an innovative dual-targeting chimeric antigen receptor (CAR) T-cell product designed to combat aggressive B-cell non-Hodgkin lymphoma. It specifically targets both CD19 and CD20 antigens. As of late October 2024, 23 patients with relapsed or refractory large B-cell lymphoma, who had not previously undergone CAR T-cell therapy, were treated with IMPT-314. Among the 17 patients who were evaluated for efficacy, the results were encouraging, showing a 94% objective response rate (ORR). Notably, 71% of these patients achieved a complete response (CR) within three months of treatment. The median follow-up period was approximately 6.3 months, during which 71% of the patients remained in response.

In terms of safety, the treatment was well-tolerated among the 23 patients in the safety evaluation group. There were no reports of high-grade cytokine release syndrome (CRS), and only 13% of patients experienced Grade 3 immune effector cell-associated neurotoxicity syndrome (ICANS), which were effectively managed using standard treatment protocols.

IMPT-314 demonstrated robust cellular expansion, with peak expansion occurring between days 7 and 28 after infusion. Importantly, the final product contained a high percentage of naïve and central memory cell phenotypes, which are associated with improved overall survival in CAR T-cell therapies.

Dr. Sarah M. Larson, who presented the data at the ASH meeting, emphasized the potential of IMPT-314 to provide a differentiated benefit over existing CD19 CAR therapies, particularly in patients with aggressive large B-cell lymphoma. The therapy incorporates the same CAR construct as CART19/20, which has shown promising results in earlier trials at UCLA.

Lyell Immunopharma’s President and CEO, Dr. Lynn Seely, expressed optimism regarding IMPT-314’s potential in providing durable responses and overcoming challenges such as heterogeneous CD19 antigen density and antigen escape. The company is on track to initiate a pivotal trial in 2025 for CAR T-naive patients with large B-cell lymphoma in later lines of treatment. Additionally, evaluations continue for its application in earlier lines of therapy as part of the ongoing trial.

IMPT-314, designed with an innovative ‘OR’ logic gate to target B cells expressing either CD19 or CD20, represents a next-generation approach in CAR T-cell therapy. The product is enriched with CD62L-expressing cells, aimed at enhancing antitumor activity. It has received Fast Track Designation from the U.S. Food and Drug Administration for treating relapsed or refractory aggressive B-cell lymphoma.

Lyell Immunopharma, headquartered in South San Francisco, is committed to advancing its pipeline of next-generation CAR T-cell therapies, with the goal of improving clinical outcomes for patients with various types of cancer. The company’s focus on developing T cells that resist exhaustion and maintain durable stemness is at the core of its strategy to achieve long-lasting tumor cytotoxicity and consistent clinical responses.