Nexcella, a subsidiary of Immix Biopharma, announced promising clinical data for its BCMA-targeted CAR-T cell therapy, NXC-201, in patients with relapsed or refractory light chain (AL) amyloidosis. The Phase 1b/2a NEXICART-1 study (NCT04720313) revealed a 100% overall response rate in patients who had relapsed or were refractory to Darzalex (daratumumab)-based regimens, addressing a critical unmet need in this challenging patient population.
The data, presented at the 26th Annual Meeting of The American Society of Gene and Cell Therapy (ASGCT), highlighted the potential of NXC-201 to provide a valuable treatment option for AL amyloidosis patients who have progressed on existing standards of care. The study included eight patients with AL amyloidosis who had previously been treated with Darzalex-based therapies.
Key Findings from the NEXICART-1 Study
The study showcased impressive efficacy and a favorable safety profile for NXC-201:
- Overall Response Rate: 100% (8/8 patients)
- Complete Response Rate: 63% (5/8 patients) with MRD negativity (10-5)
- Organ Response Rate: 75% (6/8 patients)
- Cytokine Release Syndrome (CRS): Zero grade 4 CRS events reported
- Duration of Response: The best responder had a duration of response of 16.5 months as of the data cutoff date of May 11, 2023, with the response ongoing.
Notably, 62% (5/8) of the patients had NYHA classification III or IV heart failure prior to treatment with NXC-201, indicating a severely compromised cardiac function. The rapid organ response observed is believed to be associated with a fast reduction of free light chain toxicity, a hallmark of AL amyloidosis.
Expert Commentary
"We continue to be very encouraged by NXC-201," said Polina Stepensky, M.D., Director of the Hadassah Medical Organization’s Department of Bone Marrow Transplantation and Immunotherapy for Adults and Children, and principal study investigator. "In AL amyloidosis, these data are compelling as recent trials demonstrate an overall response rate of 55% for DARZALEX-relapsed or refractory AL amyloidosis patients receiving investigator’s choice. Importantly, NXC-201 may offer a valuable option for the increasing number of AL amyloidosis patients who have progressed on DARZALEX-based standards of care."
About the NEXICART-1 Trial
The NEXICART-1 trial is an ongoing Phase 1b/2a open-label study designed to evaluate the safety and efficacy of NXC-201 in adults with relapsed or refractory multiple myeloma and AL amyloidosis. The Phase 1b portion aimed to characterize the safety and confirm the recommended Phase 2 dose (RP2D) of NXC-201, which was determined to be 800 million CAR+ T cells. The Phase 2 portion will assess efficacy and safety, with endpoints including overall survival, progression-free survival, and response rates based on International Myeloma Working Group (IMWG) criteria.
Future Plans
Nexcella plans to submit an IND application to the FDA for a Phase 1b/2 trial of NXC-201 in relapsed/refractory multiple myeloma and AL amyloidosis to expand the clinical trial to the U.S. The company intends to submit data to the FDA in multiple myeloma once 100 patients are treated with NXC-201 and in AL amyloidosis once 30-40 patients are treated.
About AL Amyloidosis
AL amyloidosis is a rare systemic disorder characterized by the abnormal production of misfolded amyloid proteins by plasma cells in the bone marrow. These proteins accumulate in tissues, nerves, and organs, leading to progressive organ damage and high mortality rates. It affects approximately 30,000 to 40,000 patients in the U.S. and Europe, with an estimated 3,000 to 4,000 new cases annually in the U.S.
