Overview

The study will evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of cevostamab in participants with systemic lupus erythematosus (SLE) with or without active lupus nephritis (LN).

Eligibility

Inclusion Criteria:

• Diagnosis of SLE according to the 2019 European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) Classification Criteria at least 6 months prior to the first screening visit
• Active biopsy-proven LN established within 9 months of screening, demonstrating LN per 2018 Revised International Society of Nephrology/Renal Pathology Society (ISN/RPS) criteria
• Diagnosis of active SLE disease, as demonstrated by the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score
• Inadequate response or intolerance to, in the investigator's judgement, standard of care regimens for active SLE with or without LN

Exclusion Criteria:

• Pregnant or breastfeeding, or intending to become pregnant during the study or within the timeframe in which contraception is required
• Treatment with investigational or non-investigational biologic therapies that directly deplete B cells (e.g., anti-CD20 or anti-CD19 monoclonal antibodies) (or blinded comparators) is prohibited within 6 months or 5 drug elimination half-lives, whichever is longer, prior to screening and during the study
• Treatment with investigational biologic therapies that do not directly deplete B cells (or blinded comparators) is prohibited within 90 days or 5 drug elimination half-lives, whichever is longer, prior to initiation of study drug and during the study
• Treatment of SLE/LN with non-investigational biologic therapies that do not directly deplete B cells (e.g., belimumab, anifrolumab) is prohibited within 4 weeks prior to screening and during the study
• Treatment with CYC within 3 months prior to screening or during the study
• History of known or suspected allergic reaction or anaphylactic reaction to cevostamab or its excipients
• Major surgery requiring hospitalization during the 4 weeks prior to screening or during screening, or any planned surgery or procedure requiring hospitalization during the 12 weeks following study drug administration
• Alcohol or substance abuse within the 12 months prior to screening
• Active infection of any kind, excluding fungal infection of the nail beds
• History of serious recurrent or chronic infection
• Tuberculosis (TB) infection
• Active overlap syndrome with mixed connective tissue disease or systemic sclerosis within the 12 months prior to screening or during screening
• Catastrophic or severe antiphospholipid syndrome within the 12 months prior to screening or during screening
• High risk for clinically significant bleeding or any condition requiring plasmapheresis, IV immunoglobulin, or acute blood product transfusions
• Active severe or unstable lupus-associated neuropsychiatric disease, which, in the opinion of the investigator, is likely to require treatment with protocol-prohibited therapies
• Non-SLE related CNS disease such as stroke, epilepsy, CNS vasculitis, or neurodegenerative disease