KYSA-1: A Study of Anti-CD19 Chimeric Antigen Receptor T-Cell (CD19 CAR T) Therapy, in Subjects With Refractory Lupus Nephritis

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by a wide spectrum of organ involvement and disease severity. Renal involvement (categorized as lupus nephritis [LN]) may occur in approximately 50% of SLE patients and is marked by proteinuria, microscopic hematuria, and varying degrees of renal insufficiency. B cells play a central role in the pathogenesis of SLE and LN, with autoantibodies developing as an early finding, and local, tissue resident B cells producing pathogenic autoantibodies and driving inflammation and tissue damage over time. CD19-targeted chimeric antigen receptor (CAR) T cells harness the ability of cytotoxic T cells to directly and specifically lyse target cells to effectively deplete B cells in the circulation and in lymphoid and potentially non-lymphoid tissues. KYV-101, a fully human anti-CD19 CAR T-cell therapy, will be investigated in adult subjects with refractory lupus nephritis.

Inclusion criteria

• Age ≥18 years
• Clinical diagnosis of SLE according to 2019 European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) classification criteria
• Biopsy-proven proliferative LN Class III or IV according to 2018 International Society of Nephrology/Renal Pathology Society (ISN/RPS) criteria
• Positive anti-nuclear antibody (ANA) (titer ≥1:80 ), anti-dsDNA (≥30 IU/mL on enzyme-linked immunosorbent assay [ELISA]), or anti-Smith at screening or by documented medical history
• Up to date on recommended vaccinations, including against coronavirus disease 2019 (COVID-19)/ severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2), per Centers for Disease Control and Prevention (CDC) or institutional guidelines for immune compromised individuals

Exclusion criteria

• Rapidly progressive glomerulonephritis; history of or currently active severe central nervous system (CNS) lupus, including cerebritis, cerebrovascular accident, and seizures
• Prior treatment with cellular immunotherapy (CAR-T) or gene therapy product directed at any target
• History of allogeneic or autologous stem cell transplant
• Evidence of active hepatitis B or hepatitis C infection
• Positive serology for HIV
• Primary immunodeficiency
• History of splenectomy
• History of stroke, seizure, dementia, Parkinson's disease, coordination movement disorder, cerebellar diseases, psychosis, paresis, aphasia, and any other neurologic disorder investigator considers would increase the risk for the subject
• Impaired cardiac function or clinically significant cardiac disease
• Previous or concurrent malignancy with the following exceptions:

• Adequately treated basal cell or squamous cell carcinoma (adequate wound healing is required prior to screening)
• In situ carcinoma of the cervix or breast, treated curatively and without evidence of recurrence for at least 3 years prior to screening
• A primary malignancy which has been completely resected, or treated, and is in complete remission for at least 5 years prior to screening