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

An Open-Label, Multicenter, Phase Ib Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Cevostamab in Patients With Systemic Lupus Erythematosus With or Without Active Lupus Nephritis

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).

Study Overview

• Status: Not yet recruiting
• Conditions: Lupus Erythematosus, Systemic
• Intervention / Treatment: Drug: Cevostamab; Drug: Tocilizumab

• Study Type: Interventional
• Enrollment (Estimated): 46
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose Escalation and Expansion; The study consists of a dose-escalation stage followed by an expansion stage. Participants in both stages will receive Cevostamab in a step-up dosing regimen, followed by a target dose.	Drug: Cevostamab; Participants will receive cevostamab IV as per the schedule given in the protocol.; Other Names: RO7187797; Drug: Tocilizumab; Tocilizumab may be used as rescue medication for participants who experience a cytokine release syndrome (CRS) event.; Other Names: Actemra/RoActemra

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Percentage of Participants with Adverse Events (AEs)	Up to approximately 52 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
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

Collaborators and Investigators

• Sponsor: Genentech, Inc.

Study record dates

Study Major Dates

• Study Start (Estimated): July 31, 2026
• Primary Completion (Estimated): March 29, 2030
• Study Completion (Estimated): March 29, 2030

Study Registration Dates

• First Submitted: June 1, 2026
• First Submitted That Met QC Criteria: June 1, 2026
• First Posted (Actual): June 5, 2026

Study Record Updates

• Last Update Posted (Actual): June 5, 2026
• Last Update Submitted That Met QC Criteria: June 1, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Skin and Connective Tissue Diseases; Lupus Erythematosus, Systemic; tocilizumab
• Other Study ID Numbers: GA46280; 2025-522904-26-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes