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

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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

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.”

REFERENCES
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. https://immpact-bio.com/news-and-events/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/
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. 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
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. https://immpact-bio.com/news-and-events/immpact-bios-impt-314-receives-fast-track-status-from-us-fda/
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. https://kyvernatx.com/press-releases/kyverna-therapeutics-announces-fda-clearance-of-ind-for-kyv-101-a-novel-fully-human-cd19-car-t-cell-therapy-to-treat-lupus-nephritis/
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. https://www.cabalettabio.com/news-media/press-releases/detail/81/cabaletta-bio-receives-fda-clearance-of-ind-application-for
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. https://www.cabalettabio.com/news-media/press-releases/detail/87/cabaletta-bio-receives-fda-clearance-of-ind-application-for
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