NXC-201 Earns FDA RMAT Designation in AL Amyloidosis
- The FDA has granted Regenerative Medicine Advanced Therapy (RMAT) designation to NXC-201 for the treatment of relapsed or refractory light chain (AL) amyloidosis.
- NXC-201 is a B-cell maturation antigen (BCMA)-targeted chimeric antigen receptor (CAR) T-cell therapy.
- A phase 1b/2 trial titled NEXICART-2 (NCT06097832)is currently enrolling
40 patients to further evaluate the efficacy and safety of NXC-201.
The FDA has granted RMAT designation to NXC-201, a BCMA-targeted CAR T-cell therapy, for the treatment of patients with relapsed or refractory AL amyloidosis.1
NXC-201 is currently under investigation for the treatment of patients with AL amyloidosis in the phase 1b/2 NEXICART-2 clinical trial. Approximately 40 patients in total are expected to be enrolled in the trial, which is taking place at study sites in California, Michigan, New York, and Ohio.
Early findings from the NEXICART-2 study have shown promise.2 As of November 2024, 4 patients enrolled in the study had normalized their disease markers within 30 days of receiving NXC-201. Two patients achieved complete responses (CR), and the other 2 achieved minimal residual disease negativity at the 10-6 sensitivity level.
For safety, hematologic toxicities, including anemia, neutropenia, thrombocytopenia, and lymphopenia, were observed, consistent with expected CAR T-cell therapy adverse events (AEs). Cytokine release syndrome (CRS) occurred in a subset of patients, with grade 1 and 2 cases being the most common, though 3 patients experienced grade 3 CRS. The median time to CRS onset was one day, and the median duration was 2 days.
Additionally, organ toxicities were reported, with 3 patients experiencing congestive heart failure, four developing acute kidney injury, and 6 showing signs of hepatic injury. Infections were another concern, as 5 patients developed febrile neutropenia, and a total of 16 patients experienced infections, either early or late post-infusion.
“Receipt of FDA RMAT designation underscores the strength of our NXC-201 data and the potential for NXC-201 to provide a new treatment option for patients with relapsed/refractory AL amyloidosis, where no drugs are FDA approved today,” said Ilya Rachman, MD, PhD, chief executive officer of Immix Biopharma, in a press release.1
Early Data on NXC-201
These findings build on data from the international, phase 1a/b NEXICART-1 trial (NCT04720313). Here, experts investigated the efficacy and safety of NXC-201 in this patient population.3 Among the 16 evaluable patients, the therapy achieved an impressive overall hematologic response rate of 94%, with 75% of patients achieving a CR.
In the NEXICART-1 trial, 13 of the 16 patients received the target dose of 800 x 106 CAR T cells, with the remaining patients receiving lower doses.2 The median age of those enrolled was 64 years, and the majority had advanced organ involvement, with the heart (81%), kidneys (69%), and peripheral nervous system (38%) being the most affected organs. Patients received a median of 4 prior lines of therapy, with 88% being refractory to triple-drug regimens including proteasome inhibitors, immunomodulatory agents, and anti-CD38 monoclonal antibodies.
Additional data from the NEXICART-1 trial showed that 62% of patients achieved an organ response. The median duration of response was 8 months, with event-free survival (EFS) and overall survival still being analyzed at the median follow-up of 8.4 months. While the EFS was reported at 9.6 months, further follow-up is needed to fully assess long-term outcomes.
“We are also pleased to report that the pace of enrollment in NEXICART-2 has accelerated, following successful completion of the safety run-in segment. We look forward to sharing further information on our progress, including an update on NEXICART-2, in the first half of 2025,” said Gabriel Morris, chief financial officer of Immix Biopharma, in the press release.1
Future Directions
The phase 1b/2 NEXICART-2 study is currently expanding and focusing on patients with preserved heart function who have not previously received BCMA-targeted therapy. The study will continue to evaluate the safety and efficacy of NXC-201 in a larger cohort and will assess primary end points of CR rate and overall response rate.1
Early enrollment data from this trial suggests a potential for the therapy in this patient population, and the pace of enrollment has accelerated following the completion of the safety run-in segment.
As the company continues to advance NXC-201’s clinical development, further updates on the progress of NEXICART-2 are expected in the first half of 2025.
REFERENCES:
Immix Biopharma receives FDA regenerative medicine advanced therapy (RMAT) designation for NXC-201, sterically-optimized CAR-T for relapsed/refractory AL amyloidosis. News release. Immix Biopharma, Inc. February 10, 2025. Accessed February 17, 2025. https://tinyurl.com/3bky6wyw
Immix Biopharma announces positive US clinical data from first four patients in NEXICART-2 US trial of sterically-optimized CAR-T NXC-201 in relapsed/refractory light chain (AL) amyloidosis. New release. Immix Biopharma, Inc. December 19, 2024. Accessed February 17, 2025. https://tinyurl.com/2cn53kmm
Lebel E, Asherie N, Kfir-Erenfeld S, et al. Efficacy and safety of anti–B-cell maturation antigen chimeric antigen receptor T-cell for the treatment of relapsed and refractory AL amyloidosis. J Clin Oncol. Published online December 9, 2024. doi:10.1200/JCO-24-02252
