Obe-cel in Severe, Refractory Systemic Lupus Erythematosus (SLE) With Active Lupus Nephritis (LN)

A Single-Arm, Open-Label, Phase II Study to Determine the Safety and Efficacy of Obecabtagene Autoleucel (Obe-cel) in Participants With Severe, Refractory Systemic Lupus Erythematosus With Active Lupus Nephritis

The purpose of this trial is to evaluate the efficacy and safety of obecabtagene autoleucel (obe-cel) administered once following lymphodepletion in participants with severe, refractory systemic lupus erythematosus (SLE) and active lupus nephritis (LN).

This is a Phase 2 study to determine the efficacy and safety of obe-cel in participants with severe, refractory SLE with active LN.

The study comprises 3 periods:

1. Screening Period: From Day -30 (+7) to Day of Enrollment

2. Treatment Period: From Day -8 to Day 1 - Participants will be evaluated to confirm eligibility for lymphodepletion, and thereafter receive lymphodepletion.

   Obe-cel Administration: If the participant's eligibility for receiving obe-cel infusion is confirmed, the participant is to receive a single obe-cel infusion on Day 1.

3. Post-treatment Period: From Day 1 to End of Study all participants will be followed up for efficacy and safety evaluation.

Inclusion Criteria:

• Willing and able to give written informed consent for participation in the study or written informed consent signed by a legal guardian or representative

• Ability and willingness to adhere to protocol's Schedule of Activities and other requirements

• Participants must be 12 to 65 years of age inclusive at the time of signing the informed consent.

• Female Participants: - a female participant is eligible to participate if she is not pregnant or breastfeeding

• Diagnosis of SLE fulfilling the 2019 European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) Classification Criteria for Systemic Lupus Erythematosus.

• Positive for at least 1 of the following autoantibodies: antinuclear antibodies (ANA), or anti-dsDNA or anti-Smith.

• Severe, Active SLE defined as:

  • SLEDAI-2K score of ≥ 8 points AND
  • Severe active LN based on a renal biopsy: Class III, IV or V (V only in combination with class III or IV)

• Refractory SLE defined as failure to previous lines of therapy

Exclusion Criteria:

• Prior treatment at any time with anti-CD19 therapy
• More than 1 acute, severe lupus-related flare during screening that needs immediate treatment and/or makes the immunosuppressive washout impossible
• Significant, likely irreversible organ damage related to SLE (e.g., end-stage renal disease) that in the opinion of the Investigator renders CD19 CAR T cell therapy unlikely to benefit the participant
• History of primary antiphospholipid antibody syndrome
• Active or uncontrolled fungal, bacterial, or viral infection
• History of malignant neoplasms unless disease free for at least 24 months
• History of heart, lung, renal, liver transplant or hematopoietic stem cell transplant