Novel NXC-201 CAR T-Cell Demonstrates Efficacy, Safety in R/R AL

Data from the phase 1/2 NEXICART-2 trial (NCT06097832), presented at the 2025 ASH Annual Meeting & Exposition, indicated that the investigational BCMA-directed CAR T-cell therapy NXC-201 elicited significant, or deep responses, in a limited cohort of patients suffering from relapsed or refractory AL amyloidosis.¹

With a cutoff of November 13, 2025, and a median follow-up of 235 days (range, 90-505), disease marker normalization of pathologic paraprotein occurred in 95% (n = 19/20) of evaluable patients. Normalization was reported at a median of 7 days.

Early and deep hematologic responses occurred in 95% (n = 19/20) of patients, with organ responses noted in 70% (n = 7/10) of those who were evaluable. Additionally, 75% of cardiac evaluable patients had a median time to response of 33 days, while 60% of patients with evaluable renal involvement responded at a median of 113 days. One patient with liver disease also experienced a response.

At day 15 after beginning treatment, one patient wrote to lead study investigator Heather J. Landau, MD, that she “never thought [she would] be feeling this strong and vibrant” following CAR T-cell infusion.

“We not only see a biomarker response, but we actually are making a difference in patients’ clinical trajectory,” Landau, bone marrow transplant specialist & cellular therapist, and director of the Amyloidosis Program at Memorial Sloan Kettering Cancer Center, stated in the presentation.

Based on independent review committee evaluation, 75% (n = 15/20) of patients had complete responses (CRs) with serum immunofixation and 24-hour urine immunofixation negativity. Four other patients showed measurable residual disease (MRD) negativity in the bone marrow and were expected to develop into CRs. One patient experienced hematologic progression at 6 months, while another died at 6 months following treatment due to a cause unrelated to study therapy.

“NXC-201 is a novel BCMA-directed CAR T-cell [therapy] that can be given safely and efficiently to this patient population who have a true unmet medical need; 100% of patients were treated with a vein-to-vein time of 14 days. All cytokine release syndrome [CRS] was low grade, and there was no neurotoxicity of any kind,” Landau said. “[Additionally], 90% of patients remain on study in hematologic remission, including 5 patients who are now out for more than 12 months. The multicenter trial is ongoing and continuing to accrue.”

According to Landau, relapsed/refractory AL amyloidosis has been reported in approximately 32,500 patients in the US, with no FDA-approved therapies for this disease. She described how NXC-201 may be a sterically optimized CAR-T construct based on 3 key modifications that decrease non-specific activation, reduce cytokine release, and enhance plasma cell binding. She also highlighted a manufacturing time of 10 days for the novel construct.

As part of the open-label, single-arm, multi-site NEXICART-2 trial, 40 patients with relapsed/refractory amyloidosis were assigned to receive various doses of NXC-201. Following the completion of the dose-escalation portion in phase 1, investigators identified a recommended dose of 450 x 10⁶ cells for dose expansion in phase 2.

The trial’s primary end points included the number of treatment-related adverse effects (TRAEs), the maximum tolerated dose, and the recommended phase 2 dose.² A key secondary end point was the percentage of patients with hematologic and organ responses per Palladini 2012 AL amyloidosis response criteria.

Patients with at least 1 prior line of treatment, including a CD38 monoclonal antibody plus a proteosome inhibitor, as well as measurable hematologic disease, were eligible for enrollment on the trial. Those with prior BCMA-directed therapy, Mayo stage 3b or NYHA class III/IV cardiac disease, or concomitant symptomatic multiple myeloma were ineligible for study entry.

Among 20 evaluable patients, the median age was 66 years, and the median number of prior lines of treatment was 4. Additionally, 55% had cardiac involvement; patients tended to have advanced cardiac disease at enrollment less often than at diagnosis.

CRS was reported in 75% of patients, although all events were grade 1 or 2. The median duration and onset of CRS were 1 day. There were no instances of neurotoxicity.

Although most patients developed neutropenia, Landau noted that 1 experienced febrile neutropenia in the absence of any infection. One patient who presented with advanced kidney disease developed worsening renal function; this patient experienced a grade 5 infection that was unrelated to study treatment.

REFERENCES

1.Landau H, Raza S, Rosenberg A, et al. First 20-patient safety and efficacy data from nexicart-2, the first U.S. trial of CAR-T in R/R light chain (AL) amyloidosis, NXC-201. Blood. 2025;146(suppl 1):696. doi:10.1182/blood-2025-696

2.Study of NXC-201 CAR-T in patients with light chain (AL) amyloidosis (NEXICART-2). ClinicalTrials.gov. Updated July 10, 2025. Accessed December 8, 2025. https://tinyurl.com/yrkcf3af