Inclusion Criteria: - Participants must have signed and dated an Institutional Review Board/ Independent Ethics Committee (IRB/IEC)-approved written informed consent form (ICF) in accordance with regulatory, local, and institutional guidelines - Participants must be ≥16 years of age at the time of signing the ICF - Meet the European League Against Rheumatism (EULAR) / American College of Rheumatology (ACR) 2019 classification criteria for systemic lupus erythematosus (SLE) - Have an inadequate response to glucocorticoids and ≥ 2 immunosuppressant therapies such as cyclophosphamide, mycophenolic acid and its derivatives, belimumab, anifrolumab, rituximab, methotrexate, azathioprine, obinutuzumab, cyclosporine, tacrolimus, or voclosporin, used for at least 3 months each. Eligibility is regardless of prior hydroxychloroquine or any anti-malarial treatment. Inadequate response is defined as a lack of response, insufficient response, or lack of sustained response after at least 3-month treatment with appropriate doses of a standard of care agent. Intolerance or contraindication may be considered as inadequate response provided it is documented and confirmed acceptable by the Adjudication Committee - Have active disease at study entry when signing ICF, defined as: - ≥ 1 British Isles Lupus Assessment Group Index (BILAG) A OR ≥ 1 BILAG B with history of SLE manifestations that would qualify for a BILAG A within the last 24 months, AND - Positive autoantibodies (at least one) to confirm diagnosis of SLE: Antinuclear antibody ≥1:160, anti-dsDNA, anti-Sm, anti-Ro (SSA), anti-La (SSB), or low complement (C3 or C4) - Participants with lupus nephritis meeting the study eligibility criteria must have had a renal biopsy per standard of care within the last 6 months indicating the presence of active Class III or IV lupus glomerulonephritis (alone or in combination with Class V) according to the 2018 Revised International Society of Nephrology/Renal Pathology Society (ISN/RPS), with < 60% interstitial fibrosis and tubular atrophy < 60% global glomerulosclerosis Exclusion Criteria: - Pregnant women - Participants enrolled in concurrent interventional clinical trials involving investigational therapies or any other clinical trial - Participant is unwilling and unable to adhere to the study visit schedule and other protocol requirements