FDA Grants Fast Track Designation to IMPT-314 for Relapsed/Refractory B-cell Lymphoma

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The FDA has granted a fast track designation to the CAR T-cell therapy IMPT-314 for the treatment of patients with B-cell–mediated malignancies.

FDA

The FDA has granted a fast track designation to the CAR T-cell therapy IMPT-314 for the treatment of patients with B-cell–mediated malignancies, including relapsed or refractory 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, who received 2 or more prior lines of systemic therapy.¹

IMPT-314 is a potential first-in-class CD19/CD20–directed CAR T-cell therapy, and results from an investigator-led phase 1 trial (NCT04007029) conducted at the University of California, Los Angeles UCLA Jonsson Comprehensive Cancer Center showed that in patients with relapse/refractory non-Hodgkin lymphoma (n = 11), the CAR T-cell therapy elicited an objective response rate of 91%, including a durable complete response (CR) rate of 73%. At a median follow-up of 20.5 months, the median progression-free survival was 18.2 months.

Notably, no patients experienced neurotoxicity or immune effector cell–associated neurotoxicity syndrome. No instances of cytokine release syndrome (CRS) above grade 1 were reported.

“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. 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,” Sumant Ramachandra, MD, PhD, president and chief executive officer of ImmPACT Bio, stated in a news release.

“IMPT-314 was specifically designed to target two 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 CRS. 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 [NCT05826535] in aggressive B-cell malignancies in the second quarter of this year.”

The planned multicenter phase 1/2 study will enroll patients at least 18 years of age with histologically confirmed aggressive non-Hodgkin lymphoma, including DLBCL NOS, DLBCL arising from follicular lymphoma, PMBCL, and HGBCL.² At least 2 prior lines of therapy will be required, including an anti-CD20 monoclonal antibody and an anthracycline-containing chemotherapy regimen. Patients with transformed follicular lymphoma must have received at least 1 of these treatment regimens after transformation to DLBCL.

Other key inclusion criteria include 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 will be excluded from enrollment if they have a history of malignancy other than non-melanoma skin cancer or carcinoma in situ; have active central nervous system involvement; have a history of cardiac lymphoma involvement; receive any systemic therapy within 2 weeks prior to enrollment or leukapheresis, except for systemic inhibitory/stimulatory immune checkpoint therapy; or undergo radiation therapy within 3 weeks of enrollment.

Phase 1 will include a 3+3 trial design, where patients will be enrolled to received IMPT-314 at a target dose of 1 x 108 cells or 3 x 108 cells as a single infusion. Phase 2 will feature a single cohort of patients who will be treated with a single infusion of IMPT-314 at the target dose determinized in phase 1.

The primary objectives of phase 1 are to assess the incidence of dose-limiting toxicities and other treatment-emergent adverse effects, determine the proportion of patients who receive the target dose, and measure the CR rate per investigator assessment. In phase 2, CR rate per investigator assessment will be the primary objective.