On December 9, 2024 Lyell Immunopharma, Inc. (Nasdaq: LYEL), a clinical-stage company advancing a pipeline of next-generation CAR T-cell therapies for patients with solid tumors or hematologic malignancies, reported initial positive clinical data from the multi-center Phase 1-2 study of IMPT-314 in patients with large B-cell lymphoma that is being presented at the 66th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting (Press release, Lyell Immunopharma, DEC 10, 2024, View Source [SID1234648922]). IMPT-314 is an autologous dual-targeting CD19/CD20 chimeric antigen receptor (CAR) T-cell product candidate being developed for patients with aggressive B-cell non-Hodgkin lymphoma.
Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:
Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing
Schedule Your 30 min Free Demo!
As of October 22, 2024 (the data cutoff for the presentation), 23 patients with relapsed or refractory (R/R), CAR T-naive large B-cell lymphoma received IMPT-314. The efficacy evaluable population consisted of 17 patients. The ORR was 94% (16/17 patients), with 71% (12/17 patients) achieving a CR by three months. The median follow up was 6.3 months (range 1.2 – 12.5 months) and 71% of patients were in response at last follow-up). In the safety evaluable population of 23 patients, no Grade 3+ CRS was reported. Grade 3 ICANS was reported in 13% (3/23) of patients with a median time to complete ICANS resolution of 5 days, and rapid improvement to Grade 2 or lower with standard therapy. In the efficacy evaluable set, 16 patients were evaluable for pharmacokinetics. IMPT-314 demonstrated robust expansion and peak cell expansion occurred between Days 7 – 28 post IMPT-314 infusion (median Tmax = 10 days). Additionally, the final drug product contained the desired naïve and central memory cell phenotype (median, 91%; range, 82 – 99%) that has been associated with improved overall survival in other CAR T cell clinical studies.
The data are being presented today at the 2024 ASH (Free ASH Whitepaper) Annual Meeting by Sarah M. Larson, M.D., Associate Professor, Department of Medicine, Medical Director, Immune Effector Cell Therapy Program, Division of Hematology/Oncology, David Geffen School of Medicine at UCLA, and the poster is available in the Investors’ section of the Company’s website.
"The high rate of complete responses with a favorable safety profile support the strong potential of IMPT-314, Lyell’s next-generation dual-targeting CAR T-cell therapy enriched for naïve and central memory T cells. 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," said Lynn Seely, M.D., Lyell’s President and Chief Executive Officer. "Based on these strong data, we remain on track to initiate a pivotal trial in 2025 of IMPT-314 in CAR T-naive patients with large B-cell lymphoma in the 3rd-line+ setting and are continuing to evaluate IMPT-314 in the 2nd-line setting in the ongoing Phase 1-2 trial."
"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 in patients with aggressive large B-cell lymphoma," stated Sarah M. Larson, M.D., Associate Professor, Department of Medicine, Medical Director, Immune Effector Cell Therapy Program, Division of Hematology/Oncology, David Geffen School of Medicine at UCLA. "IMPT-314 incorporates the same CAR construct as CART19/20 which was evaluated in a Phase 1 trial at UCLA, and I am pleased that the IMPT-314 data are consistent with our experience at UCLA."
About IMPT-314
IMPT-314 is a next-generation dual-targeting CD19/CD20 CAR T-cell product candidate designed to increase complete response rates and prolong the duration of the response as compared to the approved CD19‑targeted CAR therapies for the treatment of large B-cell lymphoma.
IMPT-314 is designed with an ‘OR’ logic gate to target B cells that express either CD19, CD20 or both. IMPT-314 is manufactured to produce a CAR T-cell product with higher proportions of naïve and central memory T cells through a proprietary process that enriches for CD62L-expressing cells. This manufacturing process is designed to generate CAR T cells with enhanced antitumor activity.
IMPT-314 has received Fast Track Designation from the U.S. Food and Drug Administration for the treatment of relapsed/refractory aggressive B-cell lymphoma.