Dr Raza on Early Safety and Efficacy Data With NXC-201 in AL Amyloidosis

"What's unique about this drug is that we have not seen any neurological toxicity. We typically see toxicities like CRS quite early [with CAR T-cell therapy]… and there were no severe CRS [events]. It's quite exciting that this is so tolerable."

Shahzad Raza, MD, a hematologist/oncologist at the Cleveland Clinic, discussed safety and efficacy data from the phase 1b/2 NEXICART-2 (NCT06097832) evaluating the autologous BCMA-targeted CAR T-cell therapy NXC-201 in relapsed/refractory light chain (AL) amyloidosis.

NEXICART-2 is the first United States clinical trial of any CAR T-cell therapy in this disease state. Preliminary findings from the phase 1 portion of the study were presented during the 2025 ASCO Annual Meeting and showed that administration of NXC-201 was safe, had a manageable toxicity profile, and resulted in rapid, deep hematologic responses in all 7 patients treated.

No neurotoxicity was observed with NXC-201, and only mild, manageable cytokine release syndrome (CRS) was reported, Raza stated, adding that this is a common complication associated with CAR T-cell therapies. All patients received infusion within 14 days of leukapheresis, and no delays in manufacturing were observed.

Among the 7 patients treated in the phase 1 portion, all experienced rapid and deep hematologic responses. The median time to first response was 7 days, and the median time to best response was 26 days. Of the 9 patients evaluable for minimal residual disease (MRD), 8 were MRD negative by day 25. The primary end point of hematologic complete response (CR) was achieved in 70% of patients, with additional patients achieving very good partial responses (VGPR). Raza noted that responses appeared durable at this early follow-up and are expected to deepen with time.

Organ responses were also observed, with 4 out of 5 evaluable patients demonstrating organ improvement. Importantly, no disease relapses or progressions had occurred at the time of reporting. Raza highlighted the unexpected tolerability of NXC-201, especially given that BCMA-directed CAR T-cell therapies used in multiple myeloma are often associated with higher rates of CRS and neurotoxicity. The absence of significant neurotoxicity and severe CRS in this cohort was a notable distinction.

Raza emphasized the potential impact of these findings, stating that the early data support further evaluation of NXC-201 as a promising therapeutic option in this historically difficult-to-treat population. He concluded that achieving rapid MRD negativity and hematologic CR with minimal toxicity represents a significant step forward in the treatment of relapsed/refractory AL amyloidosis.