To Evaluate the Effects of Cevostamab in Participants With Systemic Lupus Erythematosus With or Without Active Lupus Nephritis

• Cevostamab (Drug), also known as RO7187797: Participants will receive cevostamab IV as per the schedule given in the protocol.
• Tocilizumab (Drug), also known as Actemra/RoActemra: Tocilizumab may be used as rescue medication for participants who experience a cytokine release syndrome (CRS) event.

Primary outcomes

• Percentage of Participants with Adverse Events (AEs) [Up to approximately 52 weeks]

Secondary outcomes

• Serum Concentration of Cevostamab [Up to approximately 52 weeks]
• Area Under the Concentration-Time Curve (AUC) of Cevostamab [Up to approximately 52 weeks]
• Maximum Observed Serum Concentration (Cmax) of Cevostamab [Up to approximately 52 weeks]
• Minimum Observed Serum Concentration (Cmin) of Cevostamab [Up to approximately 52 weeks]
• Clearance (CL) of Cevostamab [Up to approximately 52 weeks]
• Volume of Distribution at Steady State (Vdss) of Cevostamab [Up to approximately 52 weeks]
• Change from Baseline in the Presence Anti-Drug Antibodies (ADAs) [Up to approximately 52 weeks]

Sex: All, ages: 18 Years to 75 Years

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

NIH grants: 2025