{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["2(2)"],"submitter":["Martinez-Lopez J"],"pubmed_abstract":["OPB-111077 is a novel, highly specific oral signal transducer and activator of transcription 3 inhibitor that has exhibited good efficacy against solid and blood cancers, including acute myeloid leukemia (AML), in preclinical models. In the present study, a phase 1b, two-stage, 3+3 dose-escalation clinical trial [dose level (DL)1 of 200 mg/day and DL2 of 250 mg/day on a once daily dose schedule in 28-day cycles] was conducted to assess the maximum tolerated dose (MTD), safety profile and the preliminary antitumor activity of OPB-111077 in patients with high-risk AML. A preliminary preclinical analysis evaluated the anti-proliferative activity of OPB-111077 in 19 patients with AML with a Vivia Biotech <i>ex vivo</i> PharmaFlow precision medicine test. A total of 12 patients were ultimately enrolled in the trial: 5 patients (42%) were treated with DL1, and 7 (58%) were escalated to DL2 of OPB-111077. Dose-limiting toxicities were not observed and the MTD was not reached. In addition, the most frequently reported treatment-emergent adverse events were nausea, vomiting and fatigue. Finally, clinical activity (overall response) was observed in 3 patients (25%). On the whole, the present study demonstrates that OPB-111077 exhibits a good safety and tolerability profile and an acceptable clinical response in patients with high-risk AML. A biomarker-driven design is useful for selecting the study population upfront."],"journal":["Medicine international"],"pagination":["7"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11208994"],"repository":["biostudies-literature"],"pubmed_title":["Biomarker‑driven phase Ib clinical trial of OPB‑111077 in acute myeloid leukemia."],"pmcid":["PMC11208994"],"pubmed_authors":["Perez-Simon JA","Acuna-Cruz E","Martinez-Sanchez P","Rojas-Rudilla JL","Bergua-Burgues JM","Pina JS","Ayala R","Gorrochategui J","De La Fuente A","Rodriguez-Veiga R","Montesinos P","Perez De Oteyza J","Paciello Coronel ML","Cano I","Primo D","Calbacho M","Boluda B","Lopez-Munoz N","Ballesteros J","Martinez-Lopez J"],"additional_accession":[]},"is_claimable":false,"name":"Biomarker‑driven phase Ib clinical trial of OPB‑111077 in acute myeloid leukemia.","description":"OPB-111077 is a novel, highly specific oral signal transducer and activator of transcription 3 inhibitor that has exhibited good efficacy against solid and blood cancers, including acute myeloid leukemia (AML), in preclinical models. In the present study, a phase 1b, two-stage, 3+3 dose-escalation clinical trial [dose level (DL)1 of 200 mg/day and DL2 of 250 mg/day on a once daily dose schedule in 28-day cycles] was conducted to assess the maximum tolerated dose (MTD), safety profile and the preliminary antitumor activity of OPB-111077 in patients with high-risk AML. A preliminary preclinical analysis evaluated the anti-proliferative activity of OPB-111077 in 19 patients with AML with a Vivia Biotech <i>ex vivo</i> PharmaFlow precision medicine test. A total of 12 patients were ultimately enrolled in the trial: 5 patients (42%) were treated with DL1, and 7 (58%) were escalated to DL2 of OPB-111077. Dose-limiting toxicities were not observed and the MTD was not reached. In addition, the most frequently reported treatment-emergent adverse events were nausea, vomiting and fatigue. Finally, clinical activity (overall response) was observed in 3 patients (25%). On the whole, the present study demonstrates that OPB-111077 exhibits a good safety and tolerability profile and an acceptable clinical response in patients with high-risk AML. A biomarker-driven design is useful for selecting the study population upfront.","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Mar-Apr","modification":"2026-06-01T21:25:29.238Z","creation":"2025-04-04T21:22:39.198Z"},"accession":"S-EPMC11208994","cross_references":{"pubmed":["38938528"],"doi":["10.3892/mi.2022.32"]}}