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

Publicat a:Medicine International. 2 (2): 7- - 2022-01-01 2(2), DOI: 10.3892/mi.2022.32

Autors: Martínez-López J; Montesinos P; López-Muñoz N; Ayala R; Martínez-Sánchez P; Gorrochategui J; Rojas-Rudilla JL; Primo D; Bergua-Burgues JM; Calbacho M; Acuña-Cruz E; Pérez-Simón JA; De La Fuente A; Pérez De Oteyza J; Rodriguez-Veiga R; Pina JS; Boluda B; Cano I; Paciello Coronel ML; Ballesteros J

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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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