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)

Genentech

Status and phase: Begins enrollment in 1 month; Phase 1

Conditions: Systemic Lupus Erythematosus

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

Study type: Interventional

Funder types: Industry

Identifiers

NCT06984341

GA45767

Details and patient eligibility

About

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.

Enrollment: 162 estimated patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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162 participants in 3 patient groups

Dose Escalation

Experimental group

Description:

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

Treatment:

Drug: Cyclophosphamide

Biological: P-CD19CD20-ALLO1 Cells

Drug: Rimiducid

Drug: Fludarabine

Dose Expansion (LN cohort)

Experimental group

Description:

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

Treatment:

Drug: Cyclophosphamide

Biological: P-CD19CD20-ALLO1 Cells

Drug: Rimiducid

Drug: Fludarabine

Dose Expansion (ERL cohort)

Experimental group

Description:

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

Treatment:

Drug: Cyclophosphamide

Biological: P-CD19CD20-ALLO1 Cells

Drug: Rimiducid