Phase 1/2 Study of Nexi-002 Autologous Multi-Antigen-Specific CD8+ T Cells for the Treatment of Relapsed or Refractory Multiple Myeloma

The NEXI-002 study is a prospective, multicenter, open-label phase 1/2 trial designed to characterize the safety, immunologic, and preliminary anti-myeloma activity of the NEXI-002 antigen specific CD8+ T cell product. Multiple myeloma (MM) is an incurable malignancy that occurs predominantly in older patients and is characterized by the growth of malignant plasma cells in the bone marrow. Despite substantial advances in therapy, virtually all patients relapse after treatment, emphasizing the unmet medical need for additional effective treatments. The NEXI-002 product is an autologous non-genetically engineered therapy of CD8+ T cells that recognize HLA 02.01-restricted peptides from the WT1, CD138, CS1, and NY-ESO-1 antigens. This T-cell product includes key memory phenotypes such as stem-like memory, central memory, and effector memory cells. Eligible patients have relapsed or refractory multiple myeloma (RRMM) who have received at least three prior lines of treatment that included at least an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 agent. Three patients were enrolled into the Safety Evaluation phase and received a single infusion of 80 million (M) to 100M cells of NEXI-002 product. In this phase of the study the primary endpoint is safety and secondary endpoints include expansion, persistence, and trafficking of the NEXI-002 cells. Bridging anti-MM treatment was permitted during the manufacture of the cellular product with a wash-out period of at least 14 days prior to lymphodepletion (LD) chemotherapy (intravenous fludarabine 30 mg/m ² and cyclophosphamide 300 mg/m ²), which was administered on Days -5, -4, and -3 prior to the infusion of the NEXI-002 product up to 72 hours later (Day1). Treatment-related adverse events, including infusion reactions, events that prolong hospitalization post infusion, CRS, and neurotoxicity (ICANS) have not developed in these patients who received the NEXI-002 product. Lymphocyte recovery to baseline levels occurred within a few days after the infusion of the NEXI-002 product, demonstrating robust CD4 and CD8 T cell reconstitution following LD chemotherapy. NEXI-002 antigen specific T cells were detected in peripheral blood (PB) by multimer staining and proliferated over time and trafficked to the bone marrow (BM). The phenotype composition of detectable antigen specific T cells at both sites maintained that of the infused product. These NEXI-002 T cells persisted in PB and BM during follow-up. T-cell receptor (TCR) sequencing assays revealed T cell clones in the NEXI-002 product that were not detected in PB of patients tested at baseline. These clones subsequently expanded and persisted over time in the PB and BM.

In conclusion, these results show that infusion of the NEXI-002 product is safe, well tolerated, and capable of generating a cell-mediated immune response that may lead to clinical activity. RNA Seq transcriptional profiling of the CD8+ T cells is planned. Additional patients have recently received NEXI-002 infusions and the trial will continue to be expanded to gain additional safety, immunologic, and clinical activity experience.