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Logic-gated CAR T Therapy Cleared for Lymphoma Trials

The CD19/CD20 dual-targeted CAR is currently under investigation in an investigator-initiated study in UCLA.

The FDA has cleared ImmPACT Bio’s investigational new drug application (IND) of its logic-gated chimeric antigen receptor (CAR) T-cell therapy IMPT-314 to be evaluated for safety and preliminary efficacy in a phase 1/2 clinical trial expected to launch in early 2023 in patients with aggressive B-cell lymphoma, including diffuse large B-cell lymphoma (DLBCL).1

"This IND clearance is a significant milestone for our company," Sumant Ramachandra, MD, PhD, president and chief executive officer, ImmPACT Bio, said in a statement.1 "Results from an investigator-led study evaluating this CAR T-cell therapy demonstrated that 70% of patients achieved a complete response with significant durability of remission. These initial efficacy results combined with the favorable safety profile show that IMPT-314 could potentially be a best-in-class treatment for patients with B-cell lymphomas. We look forward to initiating this phase 1/2 trial to help cancer patients who need new therapies."

IMPT-314 is a CD19/CD20-targeted bispecific "OR-Gate" autologous CAR T-cell therapy based off pioneering work by Yvonne Chen, PhD, associate professor, University of California, Los Angeles (UCLA). The bispecific CAR has demonstrated clinically meaningful results in an ongoing investigator-led phase 1 study at UCLA (NCT04007029) in 10 participants with non-Hodgkin lymphoma (NHL), aggressive B-cell lymphoma, DLBCL, non-indolent or refractory follicular lymphoma (FL), and mantle cell lymphoma (MCL).2 Investigators found that treated participants had a 90% overall response rate and a 70% durable complete response rate. No patients experienced neurotoxicity and cytokine release syndromewas limited to grade 1. The median progression-free survival is 18.2 months with median follow-up time of over 20 months. The study is continuing to enroll patients.

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"Dr. Chen designed this bispecific CAR to address antigen escape, which is a key challenge for current approved CD19 therapies for hematological malignancies," principal investigator of the UCLA study Sarah Larson, MD, associate clinical professor of medicine, UCLA, added to the statement.1 "We tested this anti-CD19/CD20 CAR-T cell therapy in patients with relapsed or refractory NHL and are encouraged about the potential of this therapy for patients."

ImmPACT Bio is also developing 2 other platform logic-gated CAR technologies for solid tumor indications. These are a “not”-gated, iCAR-targeted therapy for lung cancer in IND-enabling studies and another “or”-gated, transforming growth factor beta-targeted therapy for glioblastoma multiforme currently in preclinical studies.

REFERENCES
1. ImmPACT Bio announces FDA clearance of IND for novel bispecific CAR to treat aggressive B-cell lymphoma. News release. ImmPACT Bio. January 24, 2023. https://www.prnewswire.com/news-releases/immpact-bio-announces-fda-clearance-of-ind-for-novel-bispecific-car-to-treat-aggressive-b-cell-lymphoma-301728582.html
2. Larson SM, Walthers CM, Ji B, et al. CD19/CD20 bispecific chimeric antigen receptor (CAR) in naïve/memory T Cells for the treatment of relapsed or refractory non-Hodgkin lymphoma. Cancer Discov. Published online November 21, 2022. doi: 10.1158/2159-8290.CD-22-0964