biostudies-literatureAndreeff MHoffmann-La Roche, Inc. NIHMedical Research CouncilNCI NIH HHS868-76https://www.ebi.ac.uk/biostudies/studies/S-EPMC4809642biostudies-literatureUnknown22(4)<h4>Purpose</h4>RG7112 is a small-molecule MDM2 antagonist. MDM2 is a negative regulator of the tumor suppressor p53 and frequently overexpressed in leukemias. Thus, a phase I study of RG7112 in patients with hematologic malignancies was conducted.<h4>Experimental design</h4>Primary study objectives included determination of the dose and safety profile of RG7112. Secondary objectives included evaluation of pharmacokinetics; pharmacodynamics, such as TP53-mutation status and MDM2 expression; and preliminary clinical activity. Patients were divided into two cohorts: Stratum A [relapsed/refractory acute myeloid leukemia (AML; except acute promyelocytic leukemia), acute lymphoblastic leukemia, and chronic myelogenous leukemia] and Stratum B (relapsed/refractory chronic lymphocytic leukemia/smaClinical cancer research : an official journal of the American Association for Cancer ResearchResults of the Phase I Trial of RG7112, a Small-Molecule MDM2 Antagonist in Leukemia.PMC4809642MC_UU_12009/11P01 CA049639P30 CA016672P01 CA49639 and CA16672P01 CA49639CA16672G1000801cP50 CA100632Assouline SIyer SPAndreeff MRuvolo VVyas PKirschbaum MNichols GGonzalez GMMiddleton SZhi JChen GRueger RKelly KRKojima KDrummond MWBridge PStrair RYee KMartinelli GReckner MPopplewell LBowen DHuang XBlotner SGraves BJukofsky LfalseResults of the Phase I Trial of RG7112, a Small-Molecule MDM2 Antagonist in Leukemia.<h4>Purpose</h4>RG7112 is a small-molecule MDM2 antagonist. MDM2 is a negative regulator of the tumor suppressor p53 and frequently overexpressed in leukemias. Thus, a phase I study of RG7112 in patients with hematologic malignancies was conducted.<h4>Experimental design</h4>Primary study objectives included determination of the dose and safety profile of RG7112. Secondary objectives included evaluation of pharmacokinetics; pharmacodynamics, such as TP53-mutation status and MDM2 expression; and preliminary clinical activity. Patients were divided into two cohorts: Stratum A [relapsed/refractory acute myeloid leukemia (AML; except acute promyelocytic leukemia), acute lymphoblastic leukemia, and chronic myelogenous leukemia] and Stratum B (relapsed/refractory chronic lymphocytic leukemia/sma2016-01-01T00:00:00Z2016 Feb2025-04-26T00:57:52.776Z2019-03-27T03:10:24ZS-EPMC48096422645917710.1158/1078-0432.CCR-15-048110.1158/1078-0432.ccr-15-0481