Obe-cel in Adolescent [Applicable in UK Only] and Adult Severe, Refractory Systemic Lupus Erythematosus

A Single-Arm, Open-Label, Phase I Study to Determine the Safety, Tolerability and Preliminary Efficacy of Obecabtagene Autoleucel in Patients With Severe, Refractory Systemic Lupus Erythematosus

This is a Phase 1 study of obecabtagene autoleucel (obe-cel), autologous T cells engineered with a chimeric antigen receptor (CAR) targeting CD19, to establish the tolerability, safety, preliminary efficacy, and pharmacokinetics of obe-cel in patients with severe, refractory SLE.

This is a single-arm, open-label Phase 1 Study to determine the safety, tolerability, and preliminary efficacy of obe-cel in patients with severe, refractory SLE. Up to a maximum of 18 patients will be treated in a maximum of 3 dose levels.

By using the Bayesian Optimal Interval (BOIN) design for overdose control, the Sponsor will review the Safety Review Committee (SRC) and Independent Data Monitoring Committee (IDMC) recommendation and determine if a dose level is suitable for a subsequent study.

Inclusion Criteria:

-Key Inclusion Criteria-

• Women or men ≥ 18 years at screening [Spain only] or patients 12 to 65 years of age (inclusive) at the time of signing the informed consent [UK only]
• 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 one of the following autoantibodies: antinuclear antibodies (ANA) at a titer of ≥ 1:80, or anti-dsDNA (≥ 30 IU/mL) or anti-Smith (> upper limit of normal [ULN]), anti-histone or anti-chromatin (> ULN)
• Severe, refractory SLE

Exclusion Criteria:

-Key Exclusion Criteria-

• Medications

  • Within 2 months of leukapheresis: use of anti-CD20 therapy
  • Prior treatment with anti-CD19 therapy (including bispecifics), adoptive T cell therapy or any prior gene therapy product (e.g., CAR T cell therapy)
  • Immunization with a live or attenuated vaccine within 2 months of leukapheresis

• SLE and Autoimmunity:

  • Recurrent neuropsychiatric lupus or active, severe or unstable neuropsychiatric lupus within 2 years from screening
  • Diagnosis of drug-induced SLE rather than idiopathic SLE
  • Any acute, severe lupus-related flare during screening that needs immediate treatment and/or makes the immunosuppressive washout impossible; thus, making the patient ineligible for CD19 CAR T therapy as judged by the Investigator or Sponsor
  • 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 patient
  • Diagnosis of another non-SLE autoimmune disease (e.g., dermatomyositis, polymyositis, scleroderma, rheumatoid arthritis) or overlap syndrome

• Medical History:

  • History or presence of: (Within 3 months before screening visit)

    • Clinically relevant central nervous system (CNS) pathology such as epilepsy, paresis, aphasia, or stroke
    • Evidence of deep venous thrombosis or pulmonary embolism

  • History or presence of severe brain injuries, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, uncontrolled mental illness, or psychosis

  • Clinically significant, uncontrolled heart disease not due to SLE (New York Heart Association Class III or IV heart failure, uncontrolled angina, severe uncontrolled cardiac arrhythmia, or electrocardiographic evidence of acute ischemia or Grade 3 conduction system abnormalities unless the patient has a pacemaker) or a recent (within 12 months of screening) cardiac event

  • Active or uncontrolled fungal, bacterial, viral (including COVID-19), or other infection requiring systemic antimicrobials for management

  • Active or latent hepatitis B or active hepatitis C

  • Human immunodeficiency virus, human T-cell leukemia virus (HTLV)-1, HTLV-2 or syphilis positive test at screening

  • History of malignant neoplasms unless disease free for at least 24 months (basal cell or squamous cell carcinoma in situ, or in situ breast cancer on hormonal therapy allowed)

  • History of heart, lung, kidney, liver transplant or hematopoietic stem cell transplant

  • Pregnancy or lactating

• Laboratory and Organ Function:

  • Left ventricular ejection fraction < 45% (or < institute's lower limit of normal) confirmed by echocardiogram
  • Oxygen saturation (SpO2) < 90% in the absence of oxygen support
  • B cell aplasia