FDA Awards FTD of IMPT-314 for B-Cell Mediated Malignancies

The fast track designation to IMPT-314 is for the treatment of multiple types of B-cell lymphoma in patients who previously received 2 or more lines of systemic therapy.

The FDA has granted fast track designation to IMPT-314, a potential first-in-class CD19/CD20 chimeric antigen receptor (CAR) T therapy for the treatment of patients with B-cell mediated malignancies, according to ImmPACT Bio.1

The potential indications for OMPT-314include for patients with relapsed or refractory (R/R) aggressive B-cell lymphoma, diffuse large B-cell lymphoma (DLBCL) not otherwise specified (NOS), high grade B cell lymphoma (HGBCL), primary mediastinal B-cell lymphoma (PMBCL), and DLBCL arising from follicular lymphoma (FL), after 2 or more lines of systemic therapy.

"Fast track designation from the FDA underscores the serious unmet medical need in patients with aggressive B cell lymphomas and reinforces the differentiated therapeutic promise of IMPT-314," said Sumant Ramachandra, MD, PhD, president and chief executive officer of ImmPACT Bio, in a press release. "Relapsed or refractory B cell lymphomas are aggressive malignancies that despite the availability of multiple treatment options, are limited by high rates of relapse, low survival rates or serious toxicity.”

This designation is supported by promising findings from an investigator-led phase 1 study (NCT04007029) where the bispecific CD19/CD20 CAR T-cell therapy demonstrated unmatched safety and durability in patients with R/R non-Hodgkin lymphoma.

In the study, IMPT-314 yielded an objective response rate of 91%, with 73% achieving a durable complete response. With a median follow-up of 20.5 months, the median progression-free survival (PFS) was 18.2 months, Additionally, there was no neurotoxicity or immune effector cell-associated neurotoxicity syndrome observed, as well as no cytokine release syndrome above grade 1.

“IMPT-314 was specifically designed to target 2 prevalent B cell antigens, CD19 and CD20 to prolong durability and help overcome treatment resistance arising from antigen escape. In a UCLA-led investigator study, the bispecific CAR construct underlying IMPT-314 has also demonstrated unmatched safety that includes no neurotoxicity and only grade 1 cytokine release syndrome,” added Ramachandra in the press release. “We believe IMPT-314 has potential to extend duration of response with a safe, well-tolerated profile that may enhance accessibility. We look forward to dosing the first patient with IMPT-314 in our phase 1/2 trial in aggressive B-cell malignancies in the second quarter of this year."

In the planned phase 1/2 trial of IMPT-314, a 3 + 3 trial design will be utilized where patients aged 18 years and older with histologically confirmed aggressive non-Hodgkin lymphoma, including DLBCL NOS, DLBCL arising from follicular lymphoma, PMBCL, and HGBCL will be enrolled. Patients will receive IMPT-314 at a target dose of 1 x 108 cells or 3 x 108 cells as a single infusion. In phase 2, a single cohort of patients will be treated with a single infusion of IMPT-314 at the target dose established in phase 1.

Each patient will remain in the active post-treatment period for approximately 2 years and will continue in long-term follow-up for 15 years after treatment.

The trial will enroll patients aged 18 years or older with histologically confirmed aggressive non-Hodgkin lymphoma, including DLBCL NOS, DLBCL arising from follicular lymphoma, PMBCL, and HGBCL. Patients must have had at least 2 prior lines of therapy, including an anti-CD20 monoclonal antibody and an anthracycline-containing chemotherapy regimen, at least 1 measurable lesion per Lugano classification, an ECOG performance status of 0 or 1, and an absolute neutrophil count of at least 1000/µL. Patients with transformed follicular lymphoma must have received at least 1 of these treatment regimens following transformation to DLBCL.

Investigators will assess the primary end points of incidence of dose-limiting toxicities and other treatment-emergent adverse effects, the proportion of patients who receive the target dose, and they will measure the CR rate per investigator assessment in phase 1. In phase 2, the primary end point will be CR rate per investigator assessment.

The trial is expected to dose its first patient with aggressive B-cell lymphoma in Q2 2023 and plans to enroll approximately 50 patients across sites in California, Iowa, Ohio, and Utah.

1. ImmPACT Bio granted FDA fast track designation for IMPT-314 in patients with relapsed or refractory aggressive B-cell lymphoma. News release. Impact Bio. May 15, 2023. Accessed May 16, 2023. https://prn.to/42WVzda
2. Study of IMPT-314 in R/R aggressive B-cell. ClinicalTrials.gov. Updated April 24, 2023. Accessed May 16, 2023. https://clinicaltrials.gov/ct2/show/NCT05826535
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