Obe-cel in Severe, Refractory Systemic Lupus Erythematosus (SLE) With 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.

• Obecabtagene autoleucel (Biological), also known as Obe-cel: Obecabtagene autoleucel (obe-cel) given as a single infusion

Primary outcomes

• Proportion of participants who achieve complete renal response (CRR) [Month 6]: CRR is a composite endpoint

Secondary outcomes

• Proportion of participants achieving remission per Definition of Remission in SLE (DORIS) criteria [Month 6]: DORIS is a composite endpoint
• Proportion of participants achieving CRR over time [Up to Month 24]: CRR is a composite endpoint
• Time to CRR [Up to Month 24]: CRR is a composite endpoint
• Proportion of participants with Partial Renal Response (PRR) [Up to Month 24]: PRR is a composite endpoint
• Time to PRR [Up to Month 24]: PRR is a composite endpoint
• Proportion of participants achieving remission per DORIS criteria over time [Up to Month 24]: DORIS is a composite endpoint
• Time to achieving remission per DORIS criteria [Up to Month 24]: DORIS is a composite endpoint
• Time to renal flare [Up to Month 24]: Renal flare is a composite endpoint
• Proportion of participants achieving Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score of 0 over time [Up to Month 24]: SLEDAI-2K is a composite index of disease activity
• Proportion of participants achieving Lupus Low Disease Activity State (LLDAS) over time [Up to Month 24]: LLDAS is a composite endpoint
• Time to LLDAS [Up to Month 24]: LLDAS is a composite endpoint
• Time to first disease flare according to Safety of Estrogens in Lupus Erythematosus National Assessment (SELENA)-SLEDAI-2K Flare Index (SFI) post-obe-cel infusion [Up to Month 24]: SFI is a composite index to identify disease flares
• To evaluate safety of obe-cel [Up to Month 24]: Proportion of participants with adverse events (AEs)

Sex: All, ages: 12 Years to 65 Years

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