P95 First two US patients with lupus nephritis (LN) treated with anti-CD19 chimeric antigen receptor (CAR) T-cell therapy: preliminary results from the KYSA-1 phase 1, multicenter study of KYV-101

Objective

LN is a major cause of morbidity and mortality in systemic lupus erythematosus (SLE). Anti-CD19 CAR T-cell therapy has demonstrated promising safety and efficacy in refractory LN (Mackensen, Nat Med, 2022). KYV-101 is a fully human autologous anti-CD19 CAR T-cell therapy designed and demonstrated to have a favorable safety profile (Brudno, Nat Med, 2020). This is a preliminary report of KYSA-1, an ongoing US phase 1, multicenter study of KYV-101 in refractory LN (NCT05938725).

Methods

Adult patients with biopsy-proven class III or IV LN with inadequate response to ³2 conventional therapies are eligible. After apheresis and manufacturing, patients receive 3 days of lymphodepletion (LD) with fludarabine (30 mg/m²/day) and cyclophosphamide (300 mg/m²/day) starting on day –7 to –5, followed by a single infusion of KYV-101 on day 0 (dose level [DL] 1, 0.5×10⁸ CAR T cells; DL2, 1×10⁸ CAR T cells).

Results

Two patients have been treated at DL1 with 90 and 28 days of follow-up. Patient 1 is an 18-year-old female patient diagnosed with SLE at age 9 with class IV LN with persistent proteinuria refractory to multiple immunosuppressive therapies. Patient 2 is a 28-year-old female with SLE since 2021 who had failed numerous immunosuppressive therapies for persistently active class IV LN. After CAR T cell infusion, both patients experienced grade 1 cytokine release syndrome consisting of fever (patient 1 on days 5 and 6; patient 2 on days 10 and 11). No immune effector cell-associated neurotoxicity syndrome, DLTs, or serious AEs occurred. KYV-101 rapidly expanded and B cell depletion was observed with evidence of B-cell recovery observed in patient 1 starting on day 56. Both patients showed improvement in LD associated cytopenias and normalization of CRP and complement levels paralleled their clinical improvement (table 1).

Conclusion

While preliminary, these data demonstrate that KYV-101 was well tolerated with evidence of clinical improvement underscoring the potential of anti-CD19 CAR T-cell therapy for treating LN. To date, 9 autoimmune patients have been treated with KYV-101 and a phase 1/2 trial of LN in Europe, KYSA-3, is also ongoing.

Acknowledgements

This study was sponsored by Kyverna Therapeutics.