TCE Therapy Demonstrates Quick Responses for Systemic Lupus Erthematosus in Early Data

Qiubai Li, MD, PhD

A-319, a T-cell engager (TCE), demonstrated improvements in patients with severe/refractory systemic lupuserythematosus (SLE) and was well-tolerated, without evidence of cytokine release syndrome (CRS) or immune effector cell-associated neurotoxicity syndrome (ICANS).¹

These data, from a phase 1 trial (NCT06400537), were presented at the American College of Rheumatology (ACR) Convergence 2024, held November 14-19 in Washington, DC, by Qiubai Li, MD, PhD, Chief, Department of Rheumatology and Immunology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology.

“B cell depletion is very important [for treating] B cell diseases such as SLE and other B-cell related diseases. We know that the CD 19 and CD3 bispecific T-cell engager has [similar mechanisms] to CAR-T, which can deplete the B cells deeper than monoclonal antibodies such as rituximab. On the other hand, we know that the TCE is not an engineered cell, so it’s more convenient and cheaper than CAR-T,” Li told HCPLive® during the meeting.

The trial enrolled participants with moderate to severe refractory SLE to receive A-319. Participants received A-319 at 0.05μg/kg/day, on days 1, 3 and 5 by 24 hours IV infusion in week 1 and 0.3μg/kg/day, on days 1, 3 and 5 by 6 hours IV infusion in week 2.

The data are from 6 participants that received A-319, with Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) scores ranging from 8 to 16 at baseline. They had a median duration of 7.5 years (range, 0.5-10) of severe/refractory SLE. Patient 6 had severe SLE with lupus nephritis (LN) and encephalopathy, 2 had disease overlap with systemic sclerosis (patient 1) and rheumatoid arthritis (patient 2), and 5 (patients 1, 2, 4, 5, and 6) had concomitant LN.¹

The investigators found that all participants had low grade fevers related to A-319 during treatment and no other drug-related adverse events, including CRS, ICANS, myelotoxicities, hypogammaglobulinemia or infections.

Li and colleagues observed rapid CD19+ B cell depletion in peripheral blood during the first week. Patient 1 had CD19+ B cells recover to over 10% of baseline at weeks 2 and 4 and a marked decrease of anti-nuclear antibodies (ANAs), anti-dsDNA, Sm, SSA, ribosomal P protein, chromatin, SCL-70, RNP 68, and other autoantibody levels by week 8. C4 and IgE levels normalized by Day 15, and C3 and urinary total protein levels normalized by week 8.¹

SLEDAI-2K scores improved from 12 at baseline to 4 at week 8 in patient 1, 8 to 0 at week 2 in patient 2, and 16 to 4 at week 2 in patient 3.Disease Activity Score-28 scores improved 5.83 at baseline to 1.96 at week 2 in patient 2 and SLE-related vasculitis improved in patient 3 by week 2.¹

“CAR-T has its own advantages and its shortcomings, and TCE has its own advantage and shortcomings. [In the future], patients may be lucky enough to have 2 kinds of different cell therapy treatment options [for SLE],” Li said.

Another early CAR-T trial is investigating MC-1-50 chimeric antigen receptor (CAR) T cells in pediatric SLE, for which data from a phase 1/2 study were presented during October’s American Society of Nephrology (ASN) Kidney Week 2024. With doses of the CD19-targeted CAR T-cells ranging from 0.3×10^5/kg cells to 3×10^5/kg cells, there was grade 1 CRS in 9 participants (81.8%) and grade 1 ICANS in 2 participants (18.2%). In 5 participants with follow-up for over 3 months, 4 have achieved Systemic Lupus Erythematosus Responder Index (SRI-4) responses.²

REFERENCES

1. Mei C, Guan X, Wu B, et al. A-319, a CD3 X CD19 T Cell Engager (TCE), for the Treatment of Severe/Refractory SLE: Early Evidence of Rapid Reset of Disease-Specific Autoimmunity. Presented at: ACR Convergence 2024; November 14-19; Washington, DC. Abstract L12

2. Liu Q, He X, Zhang Y, Liu F, Wang J, Mao J. Safety and Efficacy of Low-Dose CD19-Targeted CAR T Cells in Refractory Pediatric Systemic Lupus Erythematosus (SLE). Presented at: ASN Kidney Week 2024; San Diego, California; October 23-26. Abstract SA-OR100