A Study to Evaluate the Safety, Tolerability, Cellular Kinetics, Pharmacodynamics, and Efficacy of P-CD19CD20-ALLO1 in Participants With Severe, Treatment-refractory Systemic Lupus Erythematosus (SLE)

NCT06984341 | Not Yet Recruiting Phase 1 FDA Drug

• 1 other identifier: GA45767
• Study Type: interventional
• Target: 162
• Locations: 1 country
• Sites: 2

Brief Summary

The purpose of this study is to evaluate the safety and tolerability of P-CD19CD20-ALLO1 in participants with highly active, severe, refractory SLE with or without lupus nephritis (LN). This study includes a dose-escalation stage followed by an expansion stage. It will also evaluate the cellular kinetics (CK), pharmacodynamics (PD), and efficacy of P-CD19CD20-ALLO1.

Conditions

Systemic Lupus Erythematosus

Keywords

Lupus Nephritis; CAR-T therapy

Outcome Measures

Primary Outcomes (2)

• Number of Participants With Dose-limiting Toxicities (DLTs) at Each Dose Level of P-CD19CD20-ALLO1

  Day 1 up to Day 29

• Number of Participants With Adverse Events (AEs)

  Up to 5 years

Secondary Outcomes (4)

• Number of Chimeric Antigen Receptor (CAR) Transgene Copies in Blood Assessed by Droplet Digital Polymerase Chain Reaction (ddPCR)

  Up to 5 years

• B-cell Levels in the Blood

  Up to 5 years

• Percentage of Participants who Achieve Sustained Drug-free Definition of Remission in SLE (DORIS)

  From Week 24 through Week 52

• Number of Participants With Anti-CAR T Antibodies

  Up to 5 years

Study Arms (3)

Dose Escalation

EXPERIMENTAL

Participants with SLE (with or without LN) will receive the following interventions and dose escalated per protocol: Biological: P-CD19CD20-ALLO1 Drug: Cyclophosphamide Drug: Fludarabine Drug: Rimiducid

Biological: P-CD19CD20-ALLO1 Cells; Drug: Cyclophosphamide; Drug: Fludarabine; Drug: Rimiducid

Dose Expansion (LN cohort)

EXPERIMENTAL

Participants with SLE (with LN) will receive the following interventions at or below the maximum tolerated dose (MTD), as determined in the dose escalation stage per protocol: Biological: P-CD19CD20-ALLO1 Drug: Cyclophosphamide Drug: Fludarabine Drug: Rimiducid

Biological: P-CD19CD20-ALLO1 Cells; Drug: Cyclophosphamide; Drug: Fludarabine; Drug: Rimiducid

Dose Expansion (ERL cohort)

EXPERIMENTAL

Participants with SLE (with ERL) will receive the following interventions at or below the maximum tolerated dose (MTD), as determined in the dose escalation stage per protocol: Biological: P-CD19CD20-ALLO1 Drug: Cyclophosphamide Drug: Fludarabine Drug: Rimiducid

Biological: P-CD19CD20-ALLO1 Cells; Drug: Cyclophosphamide; Drug: Rimiducid

Interventions

Rimiducid DRUG

Rimiducid will be used as a rescue therapy in the event of the occurrence of severe or life-threatening adverse events. It will be administered intravenously.

Dose Escalation; Dose Expansion (ERL cohort); Dose Expansion (LN cohort)

P-CD19CD20-ALLO1 Cells BIOLOGICAL

P-CD19CD20-ALLO1 cells will be administered intravenously as per the schedule specified in the protocol.

Dose Escalation; Dose Expansion (ERL cohort); Dose Expansion (LN cohort)

Cyclophosphamide DRUG

Cyclophosphamide will be administered intravenously.

Dose Escalation; Dose Expansion (ERL cohort); Dose Expansion (LN cohort)

Fludarabine DRUG

Fludarabine will be administered intravenously.

Dose Escalation; Dose Expansion (LN cohort)

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• years old
• SLE diagnosis per 2019 EULAR/ACR classification criteria ≥ 24 weeks
• Autoantibody positive and low complement at screening
• Treatment refractory: Failed ≥ 2 treatments for at least 3 months
• Highly active disease:
• SLEDAI-2K ≥ 8 (excluding alopecia, headache, and fever; additional protocol-specified requirements to enhance specificity of findings)
• BILAG-2004 cat A in ≥ 1 organ system and/or cat B in ≥ 2 organ systems (excluding constitutional, musculoskeletal, and/or mucocutaneous organ systems for category B)
• PGA score ≥ 1.0 on a 0 to 3 VAS
• For patients with lupus nephritis:
• Biopsy-proven Class III or IV (± Class V) active LN per 2018 ISN/RPS criteria within 12 months of screening
• Modified NIH activity index ≥ 1/24
• UPCR ≥ 1g/g

You may not qualify if:

• Participants who are pregnant, breastfeeding, or intend to become pregnant within the timeframe in which contraception is required
• Prior treatment with CAR T-cell therapy, B-cell-targeting T-cell-dependent bispecific antibody, gene therapy product, total body irradiation, allograft organ transplant, or hematopoietic stem cell transplant
• Significant organ impairment (renal, hepatic, cardiac, or pulmonary) or uncontrolled medical disease which, in the investigator's opinion would preclude patient participation or that may require treatment with systemic corticosteroids or immunosuppressants during the study
• Active severe or unstable neuropsychiatric disease
• Protocol-specified active or chronic infections, recent major episode of infection
• High-risk medical conditions (e.g. high bleeding risk, history of cancer, recent major surgery, history of HLH/MAS, substance abuse within the previous year)

Sponsors & Collaborators

• Genentech, Inc.: lead

Study Sites (2)

University of Alabama at Birmingham: The Kirklin Clinic

Birmingham, Alabama, 35233, United States

Location

University of Iowa

Iowa City, Iowa, 52242, United States

Location

MeSH Terms

Conditions

Lupus Erythematosus, Systemic; Lupus Nephritis

Interventions

Cyclophosphamide; fludarabine

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Glomerulonephritis; Nephritis; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Study Officials

• Clinical Trials

  Genentech, Inc.

  STUDY DIRECTOR

Central Study Contacts

Reference Study ID Number: GA45767 https://forpatients.roche.com/

CONTACT

888-662-6728 (U.S.); global-roche-genentech-trials@gene.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 14, 2025
• First Posted: May 22, 2025
• Study Start (Estimated): June 30, 2026
• Primary Completion (Estimated): November 1, 2033
• Study Completion (Estimated): November 1, 2033
• Last Updated: April 23, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)