Scientific publications

First-in-human study of JNJ-67571244, a CD33 × CD3 bispecific antibody, in relapsed/refractory acute myeloid leukemia and myelodysplastic syndrome

Mar 15, 2024 | Magazine: Clinical Translational Science

Rupa Narayan  1 , Ana Alfonso Piérola  2 , William B Donnellan  3 , Antonieta Molero Yordi  4 , Maher Abdul-Hay  5 , Uwe Platzbecker  6 , Marion Subklewe  7 , Tapan Mahendra Kadia  8 , Juan Manuel Alonso-Domínguez  9 , James McCloskey  10 , Kathryn Bradford  11 , Martin Curtis  12 , Nikki Daskalakis  11 , Christina Guttke  11 , Karim Safer  11 , Brett Hiebert  13 , Joseph Murphy  14 , Xiang Li  11 , Ken Duchin  11 , Daniel Esteban  15


Relapsed/refractory (r/r) acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) outcomes remain poor. A targeted cluster of differentiation (CD)33 × CD3 bispecific antibody, JNJ-67571244, was assessed to identify the maximum tolerated dose (MTD), recommended phase II dose (RP2D), safety and tolerability, and preliminary clinical activity in patients with r/rAML or r/rMDS.

This first-in-human, open-label, phase I, dose-escalation/dose-expansion study included patients with r/rAML or r/rMDS who were ineligible for or had exhausted standard therapeutic options. JNJ-67571244 was administered intravenously or subcutaneously using step-up dosing until ≥1 discontinuation condition was met.

Outcomes included safety/tolerability, preliminary clinical activity, and systemic pharmacokinetics and pharmacodynamics. The study was terminated after evaluating 10 dose-escalation cohorts (n = 68) and before starting dose-expansion.

Overall, 11 (16.2%) patients experienced ≥1 dose-limiting toxicity; all experienced ≥1 treatment-emergent adverse event (TEAE; treatment related: 60 [88.2%]); and 64 (94.1%) experienced ≥1 TEAE of Grade ≥3 toxicity (treatment related: 28 [41.2%]). Although some patients had temporary disease burden reductions, no responses were seen. JNJ-67571244 administration increased multiple cytokines, which coincided with incidence of cytokine release syndrome, infusion-related reactions, and elevated liver function tests.

A prolonged step-up strategy was tested to improve tolerability, though this approach did not prevent hepatotoxicity. T-cell activation following treatment suggested target engagement but did not correlate with clinical activity. Safely reaching the projected exposure level for JNJ-67571244 efficacy was not achieved, thus MTD and RP2D were not determined.

CITATION  Clin Transl Sci. 2024 Mar;17(3):e13742. doi: 10.1111/cts.13742

Our authors