An exploratory study to evaluate the safety and efficacy of autologous CAR-T cells with dual targeting of BCMA and CD19 (FKC289 Injection) in subjects with relapsed or refractory systemic light chain amyloidosis

Abstract

Abstract Background: Light-chain (AL) amyloidosis is a rare, life-threatening plasma-cell dyscrasia characterized by the deposition of misfolded monoclonal immunoglobulin light chains in vital organs—most commonly the heart and kidneys—culminating in progressive multi-organ failure. Although the anti-CD38 monoclonal antibody daratumumab, combined with cyclophosphamide–bortezomib–dexamethasone (Dara-CyBorD), has recently been approved for newly diagnosed AL amyloidosis, effective options remain limited for relapsed/refractory patients (rr-ALA). BCMA-directed CAR-T therapies can rapidly suppress circulating free light chains in plasma-cell disorders, yet emerging evidence indicates that a CD19-positive clonotypic plasma-cell sub-population may represent a chemotherapy-resistant tumor-propagating compartment, driving cellular heterogeneity and antigen-loss relapse; a bispecific CD19/BCMA CAR-T construct therefore holds promise for deeper eradication of malignant plasma cells and their secreted light chains. Consequently, we launched this exploratory, first-in-human Phase 1 trial (ChiCTR2500100410) to evaluate the safety and preliminary efficacy of the bispecific CD19/BCMA CAR-T product FKC289 in patients with rr-ALA in China. Aims: To assess the safety and efficacy of FKC289 in rr-ALA in the Chinese population. Methods: Eligible patients were aged 18-75 years with Eastern Cooperative Oncology Group performance status (ECOG) of 0-2 and experienced at least one line of therapy with CD38 monoclonal antibodies and proteasome inhibitors (PIs), etc., but failed to achieve VGPR or better status (dFLC ≥40mg/L) at the time of enrollment. It is expected to enroll 9–12 subjects, and a “3+3” dose escalation design will be adopted. The primary endpoint was the safety and tolerability of FKC289 in the treatment of rr-ALA, and to explore the maximal tolerated dose (MTD) or the recommended dose range for Phase II. Secondary endpoints were assessing efficacy and PK profile for FKC289 in rr-ALA treatment. The efficacy evaluation criteria are based on the National Comprehensive Cancer Network (NCCN) Guidelines for Systemic Light Chain Amyloidosis (2023). Results: As of the data cutoff (August 5, 2025), two patients were enrolled and received a single FKC289 infusion (1 x 10^5 CAR T cells per kg body weight) after lymphodepletion. Patient 1 was a 61-year-old male, diagnosed with ALA in Jan 25, and failed to reach VGPR after 4-cycle Dara-CyBorD, with an ECOG score of 1 and Mayo-stage 3a cardiac involvement. Hematological CR was achieved in D14. On D35, the subject experienced Grade 3 myelosuppression and improved through medical intervention on D43. No cytokine release syndrome (CRS) or immune effector cell-associated neurotoxicity syndrome (ICANS) was observed. Patient 1 demonstrated good CAR-T expansion, with a peak CAR-T expansion at day 21 and a peak vector copy number of 1.13 × 10^6 copies/μg DNA. Patient 2 was a 73-year-old male, diagnosed with ALA involving multiple organs (Mayo-stage 3a cardiac/renal/hepatological) in Feb 2024, and failed to reach VGPR after 6-cycle Dara-CyBorD, with an ECOG score of 2. Patient 2 achieved hematological complete response (CR) by D10, and reached PR for cardiac response by D14. Grade 1 CRS was observed in patient 2 on D7 and resolved after medical intervention. Summary/Conclusion: This preliminary data shows FKC289 is promising in patients with rr-ALA with reaching hematological CR rapidly. Subsequent organ response is expected with long-term follow-up.