A Phase 2, Multicenter, Open-Label Study of CC-97540 (BMS-986353), CD19-Targeted Nex-T CAR T Cells, in Participants with Active SLE (Including Lupus Nephritis) with Inadequate Response to Glucocorticoids and at Least 2 Immunosuppressants (Breakfree-SLE)

Summary of Study Intervention:

The Breakfree-SLE Clinical Trial is evaluating the safety and effectiveness of CC-97540 (CD19-targeted NEX-T CAR-T cells), an investigational chimeric antigen receptor (CAR) T cell therapy, in individuals with active systemic lupus erythematosus (SLE), including lupus nephritis (LN). A CAR is a special receptor (a structure that receives a message to act in a certain way in the body) created by scientists. CARs are made to connect with certain proteins on a cell. In CAR T cell therapy, T cells are removed from a person’s blood, and then, in a laboratory, the T cells are introduced to a CAR that teaches them to target and attack the cause of disease symptoms. Next, these T cells, now called CAR T cells, are multiplied in the laboratory and at a later time returned to the same person’s bloodstream through an infusion. CAR T cell therapy is being evaluated for use in many autoimmune conditions, including lupus, myositis, scleroderma, multiple sclerosis, and myasthenia gravis.1 Researchers believe that, when used to address SLE, CAR T cell therapy may help the body destroy malfunctioning immune cells and potentially lead to SLE improvement. Participation will last about five years and consist of three main periods (pre-treatment period, treatment period, post-treatment follow-up period). Participants will be under the supervision of an experienced rheumatologist and oncologist who have experience with cell therapies throughout the duration of the study. This trial is sponsored by Bristol Myers Squibb.

Inclusion/Exclusion Criteria:

Inclusion:

Participants must:

1. Be at least 18 years of age.
2. Have been diagnosed with SLE by a qualified physician
3. Have an inadequate response to glucocorticoids and ≥ 2 immunosuppressant therapies (such as cyclophosphamide/cytoxan, mycophenolic acid and its derivatives (for example Mycophenolate mofetil/CellCept), belimumab/Benlysta, anifrolumab/Saphnelo, rituximab, methotrexate, azathioprine/Imuran, obinutuzumab/Gazyva, cyclosporine, tacrolimus, or voclosporin/Lupkynis), used for at least 3 months each. Inadequate response is defined as a lack of response, insufficient response, or lack of sustained response after at least 3-month treatment. Intolerance or contraindication may be considered as inadequate response.
4. Have active disease at study entry, defined as:

a) ≥ 1 BILAG A (meaning severe activity in 1 or more organ system) OR ≥ 1 BILAG B (meaning moderate activity in 1 or more organ system) with history of SLE manifestations that would qualify for a BILAG A within the last 24 months (for example: moderate to severe symptoms of arthritis, increased or worsening proteinuria, rash, pleurisy or pericarditis, pleural effusion, alopecia, etc)

AND

b) Positive autoantibodies (at least one) to confirm SLE disease activity: Antinuclear antibody (ANA) ≥ 1:160, anti-double-stranded-DNA, anti-Smith, SSA (anti-Ro), SSB (anti-La), or low complement (C3 or C4).

c) Participants who qualify for the study based on active lupus glomerulonephritis must have a renal biopsy within 6 months prior to signing the ICF, and/or during the screening period, indicating the presence of active Class III or IV lupus glomerulonephritis (alone or in combination with Class V). Repeat renal biopsy may be required during screening in the event of relapse or progression to chronicity to quantify ongoing activity and irreversible damage.

5. Female patients who are women of childbearing potential must agree to use a highly effective form of contraception. Male patients with female partners of childbearing potential must use effective barrier contraception (i.e., condoms) during the study and for at least 120 days after last exposure to study drug. Also, patients may not proceed with sperm or egg donation during the study and for at least 120 days after the last exposure to study drug.

Exclusion:

1. Uncontrolled fungal, bacterial, viral (including SARS-CoV-2, Cytomegalovirus, and Epstein-Barr virus) or other infection despite appropriate antimicrobials or other infection-directed treatments.
2. Active syphilis, tuberculosis, or untreated latent tuberculosis infection, or evidence of HIV infection,
3. Class III or IV heart failure as defined by the NYHA, unstable angina, or other clinically significant cardiac disease that compromise normal cardiac function.
4. Presence or history of unresolved of clinically significant central nervous system pathology such as seizure disorder, aphasia, cerebral edema, severe brain injuries, dementia, Parkinson’s disease, Grade 3 or higher tremor, cerebellar disease, organic brain syndrome, or presence of clinically active psychosis.
5. Prior history of malignancies or lymphoproliferative disease, unless the participant has been free of the disease for ≥ 2 years. The following are allowed:

a) Basal or squamous cell carcinoma of the skin.

b) Carcinoma in situ of the cervix or breast.

c) Incidental histologic finding of prostate cancer (T1a or T1b using the tumor, nodes, metastasis clinical staging system) or prostate cancer that is curative.

d) Other completely resected Stage I solid tumor with low risk for recurrence.

e) Maintenance hormonal therapies are allowed in participants with a history of breast or prostate cancer.

6. Participant is pregnant, nursing, or breastfeeding, or intends to become pregnant during participation in the study.

7. Participant has received any prior CAR T cell therapy, genetically modified T cell therapy, or stem cell transplant.

8. Participant has received any live vaccines within 6 weeks before CC-97540 administration.

Contact Information for the Study:

Christele Felix

felixc@hss.edu

646.714.6196