IMPT-514 uses the same CAR-T construct as ImmPACT Bio’s IMPT-314, which is already under clinical evaluation for non-Hodgkin lymphoma.
ImmPACT Bio’s IMPT-514, an investigational bispecific CD19/CD20-directed chimeric antigen receptor T-cell (CAR-T) therapy, has received clearance of an investigational new drug (IND) application from the FDA for a clinical trial in patients with active, refractory systemic lupus erythematosus (SLE).1
IMPT-514 makes use of a 4-1BB costimulatory domain and consists of the same CAR construct used in ImmPACT Bio’s investigational CAR-T IMPT-314, which is currently being evaluated in an investigator-led phase 1 clinical trial (NCT04007029) at University of California, Los Angeles (UCLA), in patients with non-Hodgkin lymphoma. ImmPACT Bio also received IND clearance to evaluate IMPT-314 in a larger multicenter phase 1/2 clinical trial (NCT05826535) in patients with aggressive non-Hodgkin lymphoma in January 2023, but as of May 2023 the first patient in that trial had not yet been dosed.2,3
Safety data from IMPT-314's investigator-led trial was included in the IND submission for IMPT-514.1 As of the data cutoff, there was no neurotoxicity reported and no cytokine release syndrome (CRS) events higher than grade 1 in the patients treated. Furthermore, preclinical research has demonstrated that IMPT-514 can be manufactured from the cells of patients with SLE and lupus nephritis (LN). In vitro, the manufactured product was capable of potent destruction of autologous B-cells with only moderate release of cytokines.
Trial Name:
Modified Immune Cells (CD19/CD20 CAR-T Cells) in Treating Patients With Recurrent or Refractory B-Cell Lymphoma or Chronic Lymphocytic Leukemia
ClinicalTrials.gov Identifier:
NCT04007029
Sponsor:
Jonsson Comprehensive Cancer Center
Recruitment Contact:
Jacob Naparstek, MPH
310-206-9926
[email protected]
Estimated Completion Date:
August 1, 2024
“FDA clearance to initiate clinical development of IMPT-514, the first bispecific CD19/CD20 CAR-T therapy being investigated for the treatment of SLE, marks a pivotal milestone for our autoimmune disease clinical program,” Sumant Ramachandra, MD, PhD, the president and chief executive officer of ImmPACT Bio, said in a statement.1 “The robust data package for IMPT-514 includes compelling phase 1 safety data from an ongoing investigator-led study in lymphoma at UCLA demonstrating no neurotoxicity and only grade 1 CRS to date. We have also successfully manufactured active product with cells derived from heavily treated patients with autoimmune diseases and are encouraged with the potent autologous B-cell killing properties and limited cytokine production displayed by IMPT-514 in vitro.”
In light of the new IND clearance, ImmPACT Bio is planning to assess IMPT-512 in an open-label phase 1b/2 dose-escalation clinical trial. Criteria for participation in the trial includes a case of active, refractory SLE, prior treatment with a minimum of 2 standard of care therapies, and an SLE Disease Activity Index score (SLEDAI-2K) of 8 or greater. Furthermore, the phase 1 portion of the trial will only include patients with active proliferative LN proven via biopsy. This restriction will not be in place for patients enrolling in the phase 2 portion.
IMPT-512 is 1 of several CAR-T therapies now in development for the treatment of SLE and LN. In November 2022, Kyverna Therapeutics’ KYV-101, an investigational CD19-directed CAR-T, was cleared by the FDA for a trial in LN.4 Later on, in March 2023, Cabaletta Bio received FDA clearance of its IND application for CABA-201, an investigational CD19-directed CAR-T therapy intended to treat SLE and LN.5 CABA-201 has also received clearance from the FDA for a separate clinical trial in active idiopathic inflammatory myopathy.6
“The differentiated bispecific approach of IMPT-514 is designed for broader targeting of autoreactive B-cells with the enhanced tissue and lymphoid organ penetration characteristic of CAR T-cells,” Ramachandra continued.1 “This offers the potential for a 1-time treatment administration capable of resetting the immune response for durable remission.”
