ImmPACT Bio’s Systemic Lupus Erythematosus CAR-T Cleared for US Trial


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.

About the Phase 1 Investigator-Led Study

Trial Name:
Modified Immune Cells (CD19/CD20 CAR-T Cells) in Treating Patients With Recurrent or Refractory B-Cell Lymphoma or Chronic Lymphocytic Leukemia Identifier:

Jonsson Comprehensive Cancer Center

Recruitment Contact:
Jacob Naparstek, MPH
[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.”

1. ImmPACT Bio announces FDA clearance of IND application for bispecific CD19/CD20 CAR T therapy IMPT-514 for the treatment of refractory systemic lupus erythematosus. News release. ImmPACT Bio USA, Inc. August 15, 2023. Accessed August 16, 2023.
2. ImmPACT Bio announces FDA clearance of IND for novel bispecific CAR to treat aggressive B-cell lymphoma. News release. ImmPACT Bio USA, Inc. January 24, 2023. Accessed August 16, 2023.
3. ImmPACT Bio granted FDA fast track designation for IMPT-314 in patients with relapsed or refractory aggressive B-cell lymphoma. News release. ImmPACT Bio USA, Inc. May 15, 2023. Accessed August 16, 2023.
4. Kyverna Therapeutics announces FDA clearance of IND for KYV-101, a novel fully human CD19 CAR T-cell therapy to treat lupus nephritis. News release. Kyverna Therapeutics. November 11, 2022. Accessed August 16, 2023.
5. Cabaletta Bio receives FDA clearance of IND application for CABA-201 for treatment of systemic lupus erythematosus. News release. Cabaletta Bio, Inc. March 31, 2023. Accessed August 16, 2023.
6. Cabaletta Bio receives FDA clearance of IND application for CABA-201 for treatment of myositis. News release. Cabaletta Bio, Inc. May 16, 2023. Accessed August 16, 2023.
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