FDA Awards RMAT Designation to NXC-201 for Relapsed/Refractory AL Amyloidosis

FDA

The FDA has granted regenerative medicine advanced therapy (RMAT) designation to NXC-201 (formerly HBI0101), a CAR T-cell therapy, for the treatment of patients with relapsed or refractory AL amyloidosis, according to an announcement from Immix Biopharma, Inc.¹

The sterically-optimized, BCMA-targeted therapy elicited an overall hematologic response rate of 94% with a complete response (CR) rate of 75% in evaluable patients with relapsed/refractory AL amyloidosis (n = 16), according to data from the ex-US phase 1a/b NEXICART-1 study (NCT04720313).² The therapy is also under evaluation in the phase 1b/2 NEXICART-2 study (NCT06097832). Early data showed that all 4 patients who received the agent as of the data cutoff date of November 14, 2024, normalized their disease markers within 30 days of dosing; 2 patients were classified as having a CR and the other 2 patients achieved minimal residual disease negativity (10^-6 sensitivity) in the bone marrow.³

“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,” Ilya Rachman, MD, PhD, chief executive officer of Immix Biopharma, stated in a news release.¹

Navigating NEXICART-1

The AL subgroup of the single-arm, open-label, phase 1a/b trial included those who previously received at least 3 prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 antibody.² Patients needed to have a minimum platelet count of 30 x 10⁹ mL, creatinine clearance of 20 mL/min, left ventricular ejection fraction of 40%, and an ECOG performance status up to 2.

Fourteen patients were enrolled and infused with the therapy between September 2021 and May 2024, and 2 patients were treated on a compassionate basis. Thirteen of the 16 patients received a target dose of 800 x 10⁶ CAR T cells (range, 570 x 10⁶ to 1050 x 10⁶). One patient received bridging therapy with venetoclax (Venclexta) for 82 days between apheresis and CAR T administration. Eighty-one percent of patients received lymphodepletion comprised of fludarabine and cyclophosphamide.

The median patient age was 64 years (range, 55-82) and most were male (n = 11). Involved organs included the heart (81%), kidneys (69%), soft tissue (38%), peripheral nervous system (38%), liver (38%), gastrointestinal (31%), and lung (6%). Patients had stage I to II (69%), stage IIIa (25%), or IIIb (6%) disease per the Cardiac Mayo staging system. Most patients (75%) had an ECOG performance status of 0 or 1. The median number of prior lines of therapy received was 4 (range, 3-10) and 88% of patients were triple-drug refractory. Notably, 38% of patients were refractory to belantamab mafodotin (Blenrep) and almost all (94%) were refractory to their last line of treatment.

Sixty-two percent of patients achieved an organ response. With a median follow-up of 8.4 months (95% CI, 4-31.5), the median event-free survival (EFS) was 9.6 months (3.3-not reached [NR]), the median duration of response was 8 months (95% CI, 2-NR), and the median overall survival was 10.1 months (95% CI, 5.8-NR).

Regarding safety, hematologic toxicities included anemia (n = 12; grade 3/4, n = 5), thrombocytopenia (n = 9; n = 0), neutropenia (n = 12; n = 10), and lymphopenia (n = 16; n = 16). Cases of grade 1 (n = 3), grade 2 (n = 8), and grade 3 (n = 3) cytokine release syndrome (CRS) was reported. The median time to onset was 1 day (range, 1-3) and the median duration was 2 days (range, 1-5). Three patients experienced congestive heart failure, 4 had acute kidney injury, and 6 had hepatic injury. Regarding infections, 5 patients had febrile neutropenia, 9 had early infections, and 7 had late infections.

NEXICART-2

The open-label, single-arm, multisite phase 1b/2 dose-expansion trial is slated to enroll 40 patients with relapsed/refractory AL amyloidosis who have preserved heart function and have not previously received BCMA-targeted therapy.¹ The study comprises a safety-run in period to examine 2 doses of the CAR T-cell therapy: 150 million CAR T cells (n = 3) and 450 million CAR T cells (n = 3). The primary end points of the study are CR rate and overall response rate.

“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,” Gabriel Morris, chief financial officer of Immix Biopharma, added in the release. “We look forward to sharing further information on our progress, including an update on NEXICART-2, in the first half of 2025.”

References

1. 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 10, 2025. https://immixbio.com/immix-biopharma-receives-fda-regenerative-medicine-advanced-therapy-rmat-designation-for-nxc-201-sterically-optimized-car-t-for-relapsed-refractory-al-amyloidosis/
2. 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
3. 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 10, 2025. https://immixbio.com/immix-biopharma-announces-positive-u-s-clinical-data-from-first-four-patients-in-nexicart-2-u-s-trial-of-sterically-optimized-car-t-nxc-201-in-relapsed-refractory-light-chain-al-amyloidosis/