Preliminary analysis of a phase 1/2 study of NEXI-001 donor-derived multi-antigen-specific CD8+ T-cells for the treatment of relapsed acute myeloid leukemia (AML) after allogeneic hematopoietic cell transplantation (HCT).

Abstract

2538 Background: Allogeneic HCT is a potentially curative therapy for many patients with AML that relies on a graft-versus-leukemia (GvL) effect. Patients who relapse after allogeneic HCT have a poor prognosis and few treatment options. Donor lymphocyte infusion (DLI) can achieve a GvL effect in some patients, however, efficacy is frequently associated with the development graft-versus-host disease (GVHD). There is a substantial need for treatment approaches that enhance the benefit of GVL while decoupling toxicities associated with GVHD. Methods: We report ongoing results from a first-in-human study (NCT04284228) of a non-genetically engineered, donor-derived adoptive cellular therapy product, NEXI-001, which contains multiple populations of CD8+ T cells that recognize different HLA 02.01-restricted peptides from the WT1, PRAME, and Cyclin A1 antigens. NEXI-001 contains T cell memory subtypes that combine anti-tumor potency with long-term persistence. Results: At the time of this analysis, 7 patients with relapsed AML after allogeneic HCT were enrolled. Five Patients were treated with single infusions of NEXI-001 at three different dose levels: 50, 100 and 200 million. Currently, the median follow-up is 5 months. Significantly, GVHD, cytokine release syndrome, neurotoxicity, or NEXI-001-related adverse events were not observed. NEXI-001 treatment resulted in reductions in red blood cell and platelet transfusions and increased donor chimerism. Decreases in myeloblasts in bone marrow and peripheral blood and reduction in the size of an extramedullary myeloid sarcoma were suggestive of an anti-leukemia effect (Table). Correlative studies indicate that NEXI-001 CD8+ cells undergo a rapid proliferation after infusion and are also associated with a robust hostlymphocyte recovery that occurs as quickly Day 3 after infusion. NEXI-001 infused CD8+T cells are detectable by multimer staining in peripheral blood of patients and proliferate over time. TCR sequencing analyses determined that infused NEXI-001 cells contain T cell clones that were undetectable in the peripheral blood of patients at baseline but were detected in blood and bone marrow and persist over time. Conclusions: NEXI-001 has the potential to enhance GvL effect without the associated toxicities of GVHD, cytokine release syndrome, and neurotoxicity. Due to these encouraging results, the trial will proceed with an evaluation of repeated NEXI-001 dosing Clinical trial information: NCT04284228. [Table: see text]