Lyell Immunopharma announced positive initial clinical data from its Phase 1-2 study of IMPT-314, a dual-targeting CD19/CD20 CAR T-cell therapy, in patients with relapsed or refractory large B-cell lymphoma. The data, presented at the 66th American Society of Hematology (ASH) Annual Meeting, showed a high objective response rate (ORR) and complete response (CR) rate with a manageable safety profile in CAR T-naive patients.
High Response Rates in Heavily Pre-treated Patients
As of the data cutoff on October 22, 2024, the efficacy evaluable population consisted of 17 patients with relapsed or refractory large B-cell lymphoma who had not previously received CAR T-cell therapy. These patients had received at least two prior lines of therapy. IMPT-314 demonstrated an ORR of 94% (16/17 patients), with 71% (12/17 patients) achieving a CR by three months. With a median follow-up of 6.3 months (range 1.2 – 12.5 months), 71% of patients remained in response at the last follow-up.
Manageable Safety Profile
The safety evaluable population included 23 patients. Notably, no Grade 3 or higher cytokine release syndrome (CRS) was reported. Grade 3 immune effector cell-associated neurotoxicity syndrome (ICANS) occurred in 13% (3/23) of patients, with a median time to complete ICANS resolution of 5 days following standard therapy. These results indicate a manageable safety profile for IMPT-314 in this patient population.
Mechanism of Action and Clinical Significance
IMPT-314 is designed with an 'OR' logic gate to target B cells expressing either CD19, CD20, or both. The manufacturing process enriches for CD62L-expressing cells, resulting in a CAR T-cell product with a higher proportion of naïve and central memory T cells. This is intended to enhance antitumor activity and prolong the duration of response compared to existing CD19-targeted CAR therapies.
According to Lynn Seely, M.D., President and Chief Executive Officer of Lyell, "The high rate of complete responses with a favorable safety profile support the strong potential of IMPT-314... This product candidate was designed to maximize durable responses by overcoming heterogeneous CD19 antigen density and antigen escape, enhance CAR T cell persistence, and reduce exhaustion."
Future Plans
Based on these promising data, Lyell plans to initiate a pivotal trial of IMPT-314 in 2025 for CAR T-naive patients with large B-cell lymphoma in the 3rd-line+ setting. The company is also continuing to evaluate IMPT-314 in the 2nd-line setting in the ongoing Phase 1-2 trial.
Sarah M. Larson, M.D., Associate Professor at UCLA's David Geffen School of Medicine, stated, "The data presented today from IMPT-314 suggest the potent targeting of both CD19 and CD20 coupled with CD62L+ cell enrichment has the potential to provide differentiated benefit in objective and complete response rates over first-generation CD19 CAR therapies..."
