A Study of IMPT-514 in Active Refractory Lupus Nephritis (LN) and Systemic Lupus Erythematosus (SLE)

Lyell Immunopharma

Status and phase: Withdrawn; Phase 2; Phase 1

Conditions: Lupus Nephritis; Systemic Lupus Erythematosus

Treatments: Biological: IMPT-514

Study type: Interventional

Funder types: Industry

Identifiers

NCT06153095

MPCT-021N

Details and patient eligibility

About

This is a Phase 1/2, multi-center, open-label study evaluating the safety and efficacy of IMPT-514, a bispecific chimeric antigen receptor (CAR) targeting cluster of differentiation (CD)19 and CD20 in participants with active, refractory lupus nephritis and systemic lupus erythematosus.

IMPT-514 treatment consists of a single infusion of CAR-transduced autologous T cells administered intravenously after a lymphodepleting therapy regimen consisting of fludarabine and cyclophosphamide. Individual participants will remain in the active post-treatment period for approximately 1 year.

Participants will continue in long-term follow-up for 15 years from treatment.

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Willing and able to provide written informed consent
2. Age 18 years of age or older
3. Weight > 45 kg at enrollment
4. Adequate blood pressure control
5. On stable background therapy for autoimmune disease (LN, SLE) with stable dose of autoimmune disease medications for at least 4 weeks prior to screening
6. Diagnosis of SLE by 2019 European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) classification criteria or 2012 Systemic Lupus Collaborating Clinics (SLICC) criteria, including positive ANA or positive anti-dsDNA
7. Positive anti-nuclear antibody (ANA), anti-dsDNA (double stranded DNA) or anti-Smith antibody at screening
8. SLE participants: SLEDAI-2K ≥ 6 points, with at least 4 points on clinical, non-laboratory items
9. SLE participants: British Isles Lupus Assessment Group (BILAG) 2004 level B in 2 or more organ systems, or BILAG level A in 1 or more organ system
10. Physician Global assessment ≥ 1 on 0 to 3 visual analogue scale (VAS)
11. LN participants: Active, biopsy-proven, proliferative LN Class III or IV by 2018 International Society of Nephrology/Renal Pathology Society (ISN/RPS) criteria

Other protocol-defined criteria apply.

Exclusion criteria

1. Any clinically significant underlying illness, other than SLE and LN, which would pose a safety risk or concern, as determined by the Investigator
2. Any other systemic autoimmune condition
3. Rapidly progressive glomerulonephritis
4. Active central nervous system (CNS) lupus
5. History of allogeneic bone marrow or stem cell transplantation or solid organ transplantation
6. History of prior B cell directed cell therapy, including CAR T treatment, autologous or allogeneic, as well as prior bispecific or T cell engager therapy
7. Drug-induced SLE

Other protocol-defined criteria apply.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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0 participants in 3 patient groups

Phase 1 Lupus Nephritis

Experimental group

Description:

Administration of IMPT-514

Treatment:

Biological: IMPT-514

Biological: IMPT-514

Biological: IMPT-514

Phase 2 Lupus Nephritis

Experimental group

Description:

Administration of IMPT-514

Treatment:

Biological: IMPT-514

Biological: IMPT-514

Biological: IMPT-514

Phase 2 SLE without Lupus Nephritis

Experimental group

Description:

Administration of IMPT-514

Treatment:

Biological: IMPT-514

Biological: IMPT-514

Biological: IMPT-514