We present the results of a phase 1 study that evaluated the safety, pharmacokinetics, pharmacodynamics, immunogenicity, and preliminary disease response to cusatuzumab, a novel anti‐CD70 monoclonal antibody, in combination with azacitidine, in newly diagnosed acute myeloid leukemia Japanese participants who were not candidates for intensive treatment. In this multicenter, single‐arm study, six participants were enrolled and treated. Only in cycle 1, participants received cusatuzumab monotherapy on day 14. Subsequently, cusatuzumab was administered intravenously on days 3 and 17 at 20 mg/kg in combination with azacitidine (75 mg/m2) on days 1‐7 of each 28‐day cycle. All six participants had at least one treatment‐emergent adverse event, and the most common treatment‐emergent adverse events (all grades) were leukopenia (four participants 66.7%) and constipation (three participants 50.0%). No dose‐limiting toxicity was observed during the study period. The combination of cusatuzumab and azacitidine is generally well tolerated in Japanese participants, and further exploration of this combination is warranted. In this study, tolerability, safety, pharmacokinetics, and preliminary efficacy of cusatuzumab in combination with azacitidine were evaluated for the treatment of newly diagnosed unfit acute myeloid leukemia (AML) Japanese participants.