Background IMMU-115 (milatuzumab), a humanized antibody targeting the CD74 antigen present on antigen-presenting cells (APC), is being studied in hematological malignancies, but dysregulation of APCs may also occur in nonmalignant disorders. IMMU-115 could thus potentially help control underlying immune responses responsible for autoimmunity.
Objectives To evaluate a weekly dosing regimen of SC IMMU-115 in patients with SLE and moderately active disease.
Methods Phase I, open-label study of adults with SLE (ACR Revised Criteria) and positive ANA (titer ≥1:80) who have moderate disease activity but not severe flares (at least 2 BILAG B's, but no A's) despite standard SLE medications incuding at least 5 mg/day prednisone. Patients continued background lupus medications and received SC IMMU-115 administered for 4 consecutive weeks, with disease activity assessed by BILAG2004 and SELENA-SLEDAI every 4 weeks until week 24.
Results Ten patients (9F/1M; median age, 37; median 7 years from diagnosis) have now received 250 mg SC IMMU-115 injections once-weekly for 4 weeks. They were on prednisone (5–20 mg/day, n=10), antimalarials (n=7), and immunosupressives (n=2) with mean SLEDAI 9.6 and BILAG-B activity in the musculoskeletal (n=10), mucocutaneous (n=9), cardiorespiratory (n=1), and renal (n=1) body systems. All patients showed improvement in at least one body system, having eliminated most muscoloskeletal B's (9/10, 90%) and mucocutaneous B's (7/9, 78%) by week 8, with the single cardiorespiratory B eliminated by week 20, and the renal B vacillating between B and C over the study. Four patients developed new B-level disease after treatment at weeks 8, 12 and 20 (all cardiorespiratory) and week 24 (neuropsychiatric). Overall, mean total BILAG (scored using B=5, C=1, D/E=0) decreased 43% with treatment, while mean SLEDAI decreased 54%, with both measures still decreased at week 24 (see Figure). Nine patients had adverse events, all Grade 1–2 (mild-moderate) and predominantly injection site (N=7) or constitutional/flu-like (N=9) reactions managed with supportive medication (steroids, antihistamines, anti-pyretics). Routine safety and other laboratories (B and T cells, monocytes, dendritic cells, serum immunoglobulins, cytokines, ANA and other autoantibodies, CRP, C3) were unremarkable. One patient developed anti-IMMU-115 antibodies (HAHA) of uncertain clinical significance, resolving within 3 months. IMMU-115 serum levels with the current assay were not detectable (<0.5 μg/mL).
Conclusions SC IMMU-115 appeared safe with manageable toxicity in the first cohort of patients with SLE and moderately active disease, all of whom received 250 mg doses given weekly for 4 weeks. Already at this first planned dose level there was evidence of treatment efficacy with suppression of initial disease activity extending 24 weeks in most patients. As such, patients are currently being randomized in a double-blinded placebo-controlled expansion phase in order to confirm the activity of SC IMMU-115 in this population.
Acknowledgement Supported in part by Grant W81XWH-13–1-0392 from the U.S. Department of Defense.
Disclosure of Interest D. Wallace Grant/research support from: Immunomedics, M. Weisman: None declared, W. Wegener Employee of: Immunomedics, H. Horne Employee of: Immunomedics, D. Goldenberg Employee of: Immunomedics