Biomarker‑driven phase Ib clinical trial of OPB‑111077 in acute myeloid leukemia

Martínez‑López,Joaquín; Montesinos,Pau; López‑Muñoz,Nieves; Ayala,Rosa; Martínez‑Sánchez,Pilar; Gorrochategui,Julian; Rojas‑Rudilla,José Luis; Primo,Daniel; Bergua‑Burgues,Juan-Miguel; Calbacho,María; Acuña‑Cruz,Evelyn; Pérez‑Simón,José Antonio; De La Fuente,Adolfo; Pérez De Oteyza,Jaime; Rodriguez‑Veiga,Rebeca; Pina,José Sánchez; Boluda,Blanca; Cano,Isabel; Paciello Coronel,María Liz; Ballesteros,Juan

doi:10.3892/mi.2022.32

Biomarker‑driven phase Ib clinical trial of OPB‑111077 in acute myeloid leukemia

Authors:
- Joaquín Martínez‑López
- Pau Montesinos
- Nieves López‑Muñoz
- Rosa Ayala
- Pilar Martínez‑Sánchez
- Julian Gorrochategui
- José Luis Rojas‑Rudilla
- Daniel Primo
- Juan-Miguel Bergua‑Burgues
- María Calbacho
- Evelyn Acuña‑Cruz
- José Antonio Pérez‑Simón
- Adolfo De La Fuente
- Jaime Pérez De Oteyza
- Rebeca Rodriguez‑Veiga
- José Sánchez Pina
- Blanca Boluda
- Isabel Cano
- María Liz Paciello Coronel
- Juan Ballesteros
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Affiliations: Department of Hematology, 12 de Octubre Hospital, Instituto de Investigación Hospital 12 de Octubre (i+12), Complutense University, H12O‑CNIO Clinical Research Unit, CIBERONC, 28041 Madrid, Spain, Department of Hematology and Hemotherapy, La Fe University and Polytechnic Hospital, 46026 Valencia, Spain, Department of Hematology, 12 de Octubre Hospital, 28041 Madrid, Spain, Bioinformatics, Vivia Biotech, 28760 Madrid, Spain, VP Science, Vivia Biotech, 28760 Madrid, Spain, Department of Hematology, San Pedro de Alcántara Hospital, 10003 Cáceres, Spain, Department of Hematology, Virgen del Rocio University Hospital, Institute of Biomedicine of Sevilla (IBIS/CSIC, CIBERONC), University of Sevilla, 41013 Sevilla, Spain, Department of Hematology, MD Anderson Cancer Center, 28033 Madrid, Spain, Department of Hematology, HM Sanchinarro University Hospital, School of Medicine, University CEU San Pablo, 28050 Madrid, Spain, Vivia Biotech, 28760 Madrid, Spain
Published online on: February 22, 2022 https://doi.org/10.3892/mi.2022.32
Article Number: 7
Copyright : © Martínez‑López et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY 4.0].

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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 ex vivo 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.

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