Dose escalation study of the HLA-A2-WT1 CD3 bispecific antibody RO7283420 in relapsed/refractory acute myeloid leukemia

Hutchings, M; Korfi, K; Montesinos, P; Santoro, A; Hou, HA; Martinez-Sanchez, P; Vives, S; Galimberti, S; Chen, TY; Frigeni, M; Garciaz, S; Salamero Garcia, O; Yeh, SP; Yee, K; Esteve, J; Bajel, A; Fleming, S; Bretz, AC; Attig, J; Sun, M; Nassiri, S; Rutishauser, T; Klein, C; Ma, YM; Schnetzler, G; Vauleon, S; Yu, H; Barata, T; Richard, M; Simon, S; Hinton, H; Keshelava, N; Subklewe, M

Author(s): Hutchings, M; Korfi, K; Montesinos, P; Santoro, A; Hou, HA; Martinez-Sanchez, P; Vives, S; Galimberti, S; Chen, TY; Frigeni, M; Garciaz, S; Salamero Garcia, O; Yeh, SP; Yee, K; Esteve, J; Bajel, A; Fleming, S; Bretz, AC; Attig, J; Sun, M; Nassiri, S; Rutishauser, T; Klein, C; Ma, YM; Schnetzler, G; Vauleon, S; Yu, H; Barata, T; Richard, M; Simon, S; Hinton, H; Keshelava, N; Subklewe, M;
Details: Publication Year 2025-08,Volume 2,Issue #3,Page 100110
Journal Title: Blood Neoplasia
Publication Type: Research article
Abstract: A novel T-cell bispecific antibody (TCB), RO7283420, engaging CD3 and the HLA-A2-Wilms tumor protein 1 complex, was evaluated in this phase 1 study to characterize safety and tolerability, determine the maximum tolerated dose (MTD), and recommend a phase 2 dose for patients with relapsed/refractory acute myeloid leukemia in 2 groups: hematologic (group I, n = 57) and molecular (group 2, n = 5) relapse. In group I, 51 received RO7283420 intravenously (IV) and 6 subcutaneously. The IV doses ranged from 0.15-4 mg (flat; n = 13), 3-18 mg (step-up; n = 34) every 3 weeks, or 9 mg weekly (step-up; n = 4). The MTD was 1/3/12 mg every 3 weeks. The most frequent adverse event in the overall population was cytokine release syndrome (61.3%) with grade ≥3 recorded in 9.7% of patients. Twelve dose-limiting toxicities were reported in 11 patients and 12 (19.4%) grade 5 adverse events, including 1 hemophagocytic lymphohistiocytosis case related to RO7283420. Among the 42 efficacy-evaluable IV patients in group I, 4.8% achieved complete remission (CR), and 2.4% achieved CR with incomplete hematologic recovery. RO7283420 induced pharmacodynamic changes in peripheral blood (PB) at doses ≥1 mg, including significant T-cell activation and expansion in the PB and bone marrow (BM). Significant associations were found between blast reduction and baseline immunophenotype, including lower regulatory T cells and higher non-exhausted CD8(+) T cells in BM. Although dose escalation was discontinued because of limited efficacy and lack of an exposure-BM response relationship, the observed pharmacodynamics underscore the promising potential of this class of TCBs targeting intracellular antigens. This trial was registered at www.clinicaltrials.gov as #NCT04580121.
Publisher: Elsevier
Department(s): Haematology
Publisher's Version: https://doi.org/10.1016/j.bneo.2025.100110
Open Access at Publisher's Site: https://doi.org/10.1016/j.bneo.2025.100110
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2025-08-22 08:45:16

Last Modified: 2025-08-22 08:47:41