A phase I, single-arm, open-label, dose-escalation, multicenter study of SAR445419, an off-the-shelf, ex vivo expanded allogeneic natural killer cell product, in participants with relapsed or refractory acute myeloid leukemia

Clinical Snapshot

Key Findings

• P Value: Not applicable (descriptive analysis only)

• Effect Size: 0% clinical response rate (0/6 participants)

• Primary Outcome: No dose-limiting toxicities observed in 6 treated participants

• Nnt Or Sensitivity: Not applicable - no therapeutic benefit demonstrated

• Confidence Interval: Not reported

Clinical Application

Manufacturing and distribution feasibility demonstrated, but clinical utility remains unproven Would require TGA approval for investigational use; not currently PBS-listed. RACGP guidelines do not address NK cell therapy. Limited relevance to Australian practice given lack of efficacy Limited applicability due to lack of efficacy and small sample size; may inform future NK cell therapy development

Abstract

BACKGROUND: SAR445419 is an investigational, off-the-shelf, allogeneic NK cell therapy derived from donor peripheral blood mononuclear cells and expanded ex vivo using PM21 particles. METHODS: This multicenter, Phase 1, dose-escalation study (NCT05712278) evaluated optimal dose(s), safety, and tolerability of SAR445419 in adults (aged ≥ 18 years) with relapsed/refractory acute myeloid leukemia (R/R AML). Following lymphodepleting chemotherapy (fludarabine 30 mg/m2/day and cytarabine 2 g/m2/day for 5 days), participants received six intravenous SAR445419 (1 × 109 and 3 × 109 NK cells/dose) doses, starting with the lower dose. The primary endpoint was the incidence of dose-limiting toxicities (DLTs), and key secondary endpoints included adverse events (AEs), hematological recovery, hematopoietic stem cell transplantation, and response rate. RESULTS: Of the 12 planned participants, 7 patients were enrolled, of whom 6 received SAR445419 before sponsor decided early study termination for reasons unrelated to safety or efficacy. No DLTs were observed. All participants experienced treatment-emergent adverse events (TEAEs); six had grade ≥ 3 TEAEs; and four had serious adverse events (SAEs). Two SAR445419-related SAEs (infusion-related reactions: both grade 2) were managed with supportive care. All participants experienced grade 3 anemia and grade 4 thrombocytopenia and neutropenia. Five deaths were reported, all due to disease progression, none related to SAR445419. No clinical responses were observed. CONCLUSIONS: This study demonstrated the overall safety of off-the-shelf ex vivo expanded allogeneic NK cells in patients with R/R AML. The successful manufacturing and distribution support the feasibility of donor-derived off-the-shelf NK cells in a clinical setting. Further investigations are required to improve the clinical efficiency of NK cells.

References

1. 1.Konopleva, M., Bhatt, V. R., Mantzaris, I., Maiti, A., Gundabolu, K., Schafer, J., Jensen, K., Saleem, R., Li, Y., Drewniak, A., Bay, P., Huh, W., Yildirim, O., Abbadessa, G., Cooley, S., & Daver, N. (2026). A phase I, single-arm, open-label, dose-escalation, multicenter study of SAR445419, an off-the-shelf, ex vivo expanded allogeneic natural killer cell product, in participants with relapsed or refractory acute myeloid leukemia. Cancer Immunology, Immunotherapy. https://doi.org/10.1200/JCO.2009.24.4590