Nexcella Inc., a subsidiary of Immix Biopharma, is making strides in the development of NXC-201, a BCMA-targeted CAR-T cell therapy, for relapsed or refractory multiple myeloma and AL amyloidosis. Clinical data from the ongoing Phase 1b/2a NEXICART-1 study (NCT04720313) demonstrate promising efficacy and a manageable safety profile, suggesting potential for outpatient treatment. These findings were further supported by an editorial in Haematologica, which highlighted NXC-201's efficacy in comparison to existing FDA-approved BCMA CAR-T therapies.
High Response Rates in Multiple Myeloma
Updated clinical data, with an October 23, 2022, data cutoff, from 42 patients in the Phase 1 expansion trial revealed a 90% overall response rate (ORR) and a 59% complete response (CR) rate at the therapeutic dose of NXC-201 in relapsed/refractory multiple myeloma. Notably, all patients had previously failed at least one immunomodulatory drug, one proteasome inhibitor, and one anti-CD38 antibody, classifying them as triple-class refractory. These results suggest that NXC-201 could offer a valuable treatment option for patients with limited alternatives.
Complete Responses in AL Amyloidosis
In a cohort of eight relapsed/refractory AL amyloidosis patients, NXC-201 achieved a 100% organ response rate (cardiac, renal, liver) and a 100% complete hematologic response, with minimal residual disease (MRD) negativity at 10^-5. These data, initially presented at the 5th European CAR-T cell meeting and published in Clinical Cancer Research, underscore the potential of NXC-201 to address the unmet needs in this rare and often fatal disease.
Outpatient Treatment Potential
Additional data indicate that NXC-201 may be suitable for outpatient administration. In the multiple myeloma cohort, the median onset of cytokine release syndrome (CRS) was on day zero, with a median duration of one day. There were no grade 4 CRS events and only one grade 3 CRS event observed across the 42 patients. This favorable safety profile could enable treatment in community hospitals, expanding access to CAR-T therapy for a broader patient population.
Editorial Highlights
An editorial by Maria Sjöstrand and Michel Sadelain of Memorial Sloan Kettering Cancer Center, published in Haematologica, emphasized the potential of NXC-201 in the context of existing BCMA CAR-T cell therapies. The authors noted that NXC-201 demonstrated a good safety profile, similar to other BCMA CAR-T cell phase I-II studies, and comparable efficacy, albeit with shorter follow-up, to that initially reported with ide-cel (Abecma) and cilta-cel (Carvykti). The editorial also pointed out that the NXC-201 trial included patients who had relapsed after belantamab mafodotin treatment, a factor that may be associated with less favorable responses to CAR-T therapy.
The expected therapeutic dose of NXC-201 is 800 million CAR+ T cells, which has already been established as the recommended Phase 2 dose (RP2D) for both multiple myeloma and AL amyloidosis. Nexcella anticipates enrolling a total of 100 patients to seek FDA BLA approval.
