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A targeted cluster of differentiation (CD)33\u2009\u00d7\u2009CD3 bispecific antibody, JNJ\u201067571244, 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\u2010in\u2010human, open\u2010label, phase I, dose\u2010escalation\/dose\u2010expansion study included patients with r\/rAML or r\/rMDS who were ineligible for or had exhausted standard therapeutic options. JNJ\u201067571244 was administered intravenously or subcutaneously using step\u2010up dosing until \u22651 discontinuation condition was met. Outcomes included safety\/tolerability, preliminary clinical activity, and systemic pharmacokinetics and pharmacodynamics. The study was terminated after evaluating 10 dose\u2010escalation cohorts (<jats:italic>n<\/jats:italic>\u2009=\u200968) and before starting dose\u2010expansion. Overall, 11 (16.2%) patients experienced \u22651 dose\u2010limiting toxicity; all experienced \u22651 treatment\u2010emergent adverse event (TEAE; treatment related: 60 [88.2%]); and 64 (94.1%) experienced \u22651 TEAE of Grade \u22653 toxicity (treatment related: 28 [41.2%]). Although some patients had temporary disease burden reductions, no responses were seen. JNJ\u201067571244 administration increased multiple cytokines, which coincided with incidence of cytokine release syndrome, infusion\u2010related reactions, and elevated liver function tests. A prolonged step\u2010up strategy was tested to improve tolerability, though this approach did not prevent hepatotoxicity. T\u2010cell activation following treatment suggested target engagement but did not correlate with clinical activity. Safely reaching the projected exposure level for JNJ\u201067571244 efficacy was not achieved, thus MTD and RP2D were not determined.<\/jats:p>","DOI":"10.1111\/cts.13742","type":"journal-article","created":{"date-parts":[[2024,3,18]],"date-time":"2024-03-18T07:25:27Z","timestamp":1710746727000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["First\u2010in\u2010human study of <scp>JNJ<\/scp>\u201067571244, a <scp>CD33<\/scp> \u00d7 <scp>CD3<\/scp> bispecific antibody, in relapsed\/refractory acute myeloid leukemia and myelodysplastic syndrome"],"prefix":"10.1111","volume":"17","author":[{"given":"Rupa","family":"Narayan","sequence":"first","affiliation":[{"name":"Division of Hematology\/Oncology, Department of Medicine Massachusetts General Hospital, Center for Leukemia  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Alfonso","family":"Pi\u00e9rola","sequence":"additional","affiliation":[{"name":"Cl\u00ednica Universidad de Navarra Pamplona  Pamplona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William B.","family":"Donnellan","sequence":"additional","affiliation":[{"name":"Hematology\/Medical Oncology Tennessee Oncology\/Sarah Cannon Research Institute  Nashville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonieta Molero","family":"Yordi","sequence":"additional","affiliation":[{"name":"Experimental Hematology Unit, Department of Hematology Vall d'Hebron Institute of Oncology (VHIO), University Hospital Vall d'Hebron  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1041-7689","authenticated-orcid":false,"given":"Maher","family":"Abdul\u2010Hay","sequence":"additional","affiliation":[{"name":"Division of Hematology &amp; 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