A Study to Evaluate the Safety and Preliminary Efficacy of ATA3219 in Participants With Systemic Lupus Erythematosus

Prior treatment

• Has a concurrent systemic autoimmune disease that may confound study assessments other than SLE, LN, or cutaneous lupus erythematosus.
• Has any unstable or progressive manifestation of SLE that is likely to warrant an intensification of lupus-directed therapy
• Has a history of catastrophic antiphospholipid syndrome, or any history of prior thrombosis due to antiphospholipid syndrome resulting in hospitalization due to myocardial infarction, pulmonary embolism, or stroke.
• Has a history of bleeding disorder requiring hospitalization or systemic therapeutic intervention within the previous 3 months, or for participants without a prior kidney biopsy meeting eligibility criterion within the past 6 months who will require a biopsy during screening, any contraindication to kidney biopsy.
• Any prior cellular therapies, obinutuzumab, anti-cluster of differentiation 19 (CD19) antibody, or B-cell targeting bispecific antibody, unless B-cells have recovered to baseline as assessed by the investigator. Investigational therapies or initiation of new SLE-directed therapies within 4 weeks.
• Any inability to discontinue or taper systemic SLE therapy prior to infusion of ATA3219, including
  • Tapering of corticosteroids to ≤ 10 mg/day and
  • Discontinuation of other systemic SLE therapies (including mycophenolate and/or voclosporin)
• Any inability to discontinue or taper systemic SLE therapy prior to infusion of ATA3219, including
  • Tapering of corticosteroids to ≤ 20 mg/day by Day -2, and
  • Suspension of other systemic SLE therapies (including mycophenolate and/or voclosporin)

Other illness

• Presence of clinically relevant (as assessed by the investigator) central nervous system (CNS) pathology such as epilepsy, seizure, aphasia, stroke, severe brain injuries, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, or psychosis; any BILAG A CNS manifestation within 4 weeks of enrollment.
• Severe kidney disease as assessed locally, defined as history of ISN/RPS Class VI or isolated Class V glomerulonephritis (without co existent/predominant Class III or IV glomerulonephritis) on renal biopsy.
• Known hypersensitivity to fludarabine or cyclophosphamide.
• Severe kidney disease as assessed locally, defined as history of ISN/RPS Class III to IV on renal biopsy.

Other

• Contraindication to methylprednisolone 500 mg daily for 2 days.

• Diagnosed with SLE according to the 2019 European League Against Rheumatism/American College of Rheumatology classification for SLE OR the Systemic Lupus International Collaborating Clinics Classification criteria [Petri 2012].
• Meets one or more of the following immunologic criteria during screening:
  • Anti double stranded DNA above laboratory reference range, except enzyme linked immunosorbent assay (2 × above laboratory reference range), OR
  • Presence of one or more of following autoantibodies: anti-Smith, anti-ribonucleoprotein, or anti-phospholipid, OR
  • Low complement as demonstrated by low complement component 3, low complement component 4, or low complement CH50.
• Adequate lung, liver, kidney, and cardiac function.
• History of International Society of Nephrology (ISN)/Renal Pathology Society (RPS) Class III or IV with or without Class V glomerulonephritis on renal biopsy either within 6 months prior to screening or as performed during screening. Biopsy should demonstrate evidence of active nephritis.
• Proteinuria level between ≥ 1.0 to 6.0 g/g via urine protein creatinine ratio during screening.
• Has refractory LN defined as having received 1 or more standard therapies for LN (which must have included mycophenolate mofetil, mycophenolic acid, or cyclophosphamide), and:
  • Has worsening LN (per criteria listed in [Gordon 2009]) while on treatment, OR
  • Has not achieved a complete renal response (CRR) after 2 or more lines of therapy, OR
  • Has not achieved a CRR after first-line therapy after a minimum of 12 months.
• Hybrid SELENA-SLEDAI score of ≥ 8 points at screening
  • For participants with BILAG A involvement, this must include "clinical" hybrid SELENA-SLEDAI score of ≥ 4 points
  • For participants without BILAG A involvement, this must include clinical hybrid SELENA-SLEDAI score of ≥ 6 points
• Meets BILAG-2004 criteria: At least 1 of the following:
  • BILAG-2004 level A disease in ≥ 1 organ system
  • BILAG-2004 level B disease in ≥ 2 organ systems and physician global assessment score ≥ 2
• Persistent disease activity as defined in inclusion criterion #8 (above), despite having received 2 or more standard-of-care immunosuppressive therapies for SLE (as determined by the investigator), which may include biologics, for a minimum of 3 months (for participants with BILAG A involvement in any organ systems) or a minimum of 6 months (for participants with only BILAG B involvement in ≥ 2 organ systems).