Logic-gated CAR T Therapy Cleared for Lymphoma Trials

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