Alnuctamab treatment for refractory SLE

Open-label, 4-Part Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of Alnuctamab (BMS-986349/CC-93269) in Participants With Moderate to Severe Refractory Systemic Lupus Erythematosus

This trial will test whether the experimental T-cell engager alnuctamab is safe and helps adults 18–60 with moderate-to-severe SLE that has not responded to standard treatments.

Quick facts

• Phase: PHASE1
• Study type: Interventional
• Enrollment: 21 (estimated)
• Ages: 18 Years to 60 Years
• Sex: All
• Sponsor: Icahn School of Medicine at Mount Sinai (other)
• Drugs / interventions: anifrolumab, belimumab, methotrexate, cyclophosphamide, alnuctamab, Alnuctumab
• Locations: 1 site (New York, New York)
• Trial ID: NCT07219563 on ClinicalTrials.gov

What this trial studies

Alnuctamab is a bispecific T-cell engager that binds BCMA on plasma B cells and redirects cytotoxic T cells to remove autoantibody-producing cells. This Phase 1, single-site study at Icahn School of Medicine at Mount Sinai will enroll adults with moderate-to-severe SLE refractory to corticosteroids and multiple immunosuppressive therapies. The primary focus is on safety, tolerability, and identifying an appropriate dose, with secondary measures of disease activity and biomarker changes. Participants will receive alnuctamab and undergo frequent clinical and laboratory monitoring for adverse events and effects on autoantibodies and SLE activity.

Who should consider this trial

Good fit: Ideal candidates are adults 18–60 with confirmed SLE by ACR/EULAR criteria who have moderate-to-severe disease that is refractory to corticosteroids and at least two immunosuppressive therapies, including prior biologic therapy or cyclophosphamide.

Not a fit: Patients with mild or well-controlled SLE, those outside the 18–60 age range, or those with contraindications to T-cell–engaging therapies are unlikely to benefit from this trial.

Why it matters

Potential benefit: If successful, this approach could reduce autoantibody-producing plasma cells and offer a new treatment option for people with severe, treatment-resistant SLE.

How similar studies have performed: This is the first clinical test of alnuctamab in SLE; BCMA-targeting approaches have shown promise in plasma-cell cancers like multiple myeloma but have limited prior testing in lupus.

Eligibility criteria

Key Inclusion Criteria:

* Age 18-60 years.
* Documented diagnosis of SLE fulfilling 2019 ACR/EULAR criteria.
* Historical documentation of ANA (1:80 or greater) autoantibody on immunofluorescence as well as presence of at least 1 additional autoantibody of the type: anti-dsDNA, anti-histone, anti-chromatin, anti-Smith, anti-RNP, anti-Ro/SSA, anti-La/SSB, anti-cardiolipin (IgG), or anti-beta2-glycoprotein1 (IgG).
* History of SLE that is refractory to corticosteroids and at least 2 immunosuppressive therapies with different mechanisms of action (methotrexate, thiopurines, mycophenolate mofetil, calcineurin inhibitors, biologic agents, cyclophosphamide), including at least one biologic therapy (e.g. anti-CD20 therapy, anifrolumab, belimumab) or cyclophosphamide. Of note, hydroxychloroquine is not considered an immunosuppressive therapy, and methotrexate/azathioprine counts as a single drug class).
* Total SLEDAI-2K \>6 with clinical SLEDAI-2K \>4, or \>1 BILAG A organ domain score, or \>2 BILAG B, but without active central nervous system (CNS) disease within the past year; a maximum of two participants with only arthritis and/or rash can be included if truly disabling

Key Exclusion Criteria:

* Autoimmune disease other than SLE, except associated Sjogren's Disease if not primary contributor to symptoms; coexistent fibromyalgia will be allowed if not primary contributor to symptoms.
* TTP-like SLE; catastrophic APS; LN WHO class V as primary qualifying criterion (unless overlap with Class III or IV), rapidly progressive LN, or eGFR \<40 mL/min; active CNS pathology attributable to neuropsychiatric SLE.
* Active or suspected infection, including HIV.
* O2 sat \<92% on room air; ANC \<1500u/L, Hgb \<8g/dL, Plt \<75,000/uL; ALT or AST \> 2X ULN (unless attributed to active myositis), Total Bilirubin \>1.5 X ULN (unless Gilbert's Disease), total B cell count \<12/microliter, hypogammaglobinemia \<500mg/dL.

Where this trial is running

New York, New York

• Icahn School of Medicine at Mount Sinai — New York, New York, United States (RECRUITING)

Study contacts

• Principal investigator: Chrisanna Dobrowolski, MD — Icahn School of Medicine at Mount Sinai School
• Study coordinator: Chrisanna Dobrowolski, MD

Conditions: Systemic Lupus Erythematosus, Refractory, Systemic Lupus Erythematosus, Severe Refractory Systemic Lupus Erythematosus