Clinical trial NCT06984341: 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)
Official title: A Phase I, Multicenter, Open-label Study to Evaluate the Safety, Tolerability, Cellular Kinetics, Pharmacodynamics, and Efficacy of P-CD19CD20-ALLO1 in Patients With Severe, Treatment-refractory Systemic Lupus Erythematosus
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE1
Conditions: Systemic Lupus Erythematosus
Keywords: Lupus Nephritis
CAR-T therapy
Lead sponsor: Genentech, Inc.
Sponsor class: INDUSTRY
First posted: 2025-05-22
Enrollment: 162
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


Eligibility criteria: Key Inclusion criteria:

18-75 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

Key Exclusion criteria:

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)

Other protocol-defined inclusion/exclusion criteria apply

Primary outcomes:
measure: Number of Participants With Dose-limiting Toxicities (DLTs) at Each Dose Level of P-CD19CD20-ALLO1
timeFrame: Day 1 up to Day 29
measure: Number of Participants With Adverse Events (AEs)
timeFrame: Up to 5 years
Secondary outcomes:
measure: Number of Chimeric Antigen Receptor (CAR) Transgene Copies in Blood Assessed by Droplet Digital Polymerase Chain Reaction (ddPCR)
timeFrame: Up to 5 years
measure: B-cell Levels in the Blood
timeFrame: Up to 5 years
measure: Percentage of Participants who Achieve Sustained Drug-free Definition of Remission in SLE (DORIS)
timeFrame: From Week 24 through Week 52
measure: Number of Participants With Anti-CAR T Antibodies
timeFrame: Up to 5 years
Other outcomes:
Locations:
Study officials:
affiliation: Genentech, Inc.
name: Clinical Trials
role: STUDY_DIRECTOR
References: