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It is being evaluated for the treatment of myeloid malignancies in the STIMULUS clinical trial program. The objective of this analysis was to support the sabatolimab dose\u2010regimen selection in hematologic malignancies. A population pharmacokinetic (PopPK) model was fit to patients with solid tumors and hematologic malignancies, which included acute myeloid leukemia, myelodysplastic syndrome (including intermediate\u2010, high\u2010, and very high\u2010risk per Revised International Prognostic Scoring System), and chronic myelomonocytic leukemia. The PopPK model, together with a predictive model of sabatolimab distribution to the bone marrow and binding to TIM\u20103 was used to predict membrane\u2010bound TIM\u20103 bone marrow occupancy. In addition, the total soluble TIM\u20103 (sTIM\u20103) kinetics and the pharmacokinetic (PK) exposure\u2010response relationship in patients with hematologic malignancies were examined. At intravenous doses above 240\u2009mg Q2w and 800\u2009mg Q4w, we observed linear PK, a plateau in the accumulation of total sTIM\u20103, and a flat exposure\u2010response relationship for both safety and efficacy. In addition, the model predicted membrane\u2010bound TIM\u20103 occupancy in the bone marrow was above 95% in over 95% of patients. Therefore, these results support the selection of the 400\u2009mg Q2w and 800\u2009mg Q4w dosing regimens for the STIMULUS clinical trial program.<\/jats:p>","DOI":"10.1002\/psp4.12962","type":"journal-article","created":{"date-parts":[[2023,4,26]],"date-time":"2023-04-26T05:34:31Z","timestamp":1682487271000},"page":"1653-1665","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Sabatolimab (<scp>MBG453<\/scp>) model\u2010informed drug development for dose selection in patients with myelodysplastic syndrome\/acute myeloid leukemia and solid tumors"],"prefix":"10.1002","volume":"12","author":[{"given":"Siyan","family":"Xu","sequence":"first","affiliation":[{"name":"Novartis Institutes for BioMedical Research  Cambridge Massachusetts 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