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Background <p>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.</p> Methods <p>This multicenter, Phase 1, dose-escalation study (NCT05712278) evaluated optimal dose(s), safety, and tolerability of SAR445419 in adults (aged ≥ 18&#xa0;years) with relapsed/refractory acute myeloid leukemia (R/R AML). Following lymphodepleting chemotherapy (fludarabine 30&#xa0;mg/m<sup>2</sup>/day and cytarabine 2&#xa0;g/m<sup>2</sup>/day for 5&#xa0;days), participants received six intravenous SAR445419 (1 × 10<sup>9</sup> and 3 × 10<sup>9</sup> 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.</p> Results <p>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.</p> Conclusions <p>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.</p>

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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

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  • 发表日期：

    2026年4月11日

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  • Marina Konopleva,
  • Vijaya Raj Bhatt,
  • Ioannis Mantzaris,
  • Abhishek Maiti,
  • Krishna Gundabolu,
  • Jolie Schafer,
  • Kyle Jensen,
  • Rao Saleem,
  • Yi Li,
  • Agata Drewniak,
  • Pierre Bay,
  • Winston Huh,
  • Ozlem Yildirim,
  • Giovanni Abbadessa,
  • Sarah Cooley,
  • Naval Daver

摘要

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.