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

• Published in: Medicine international (London) Vol. 2; no. 2; p. 7
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: England D.A. Spandidos 01.03.2022
• Subjects: OPB-111077; maximum tolerated dose; relapsed/refractory acute myeloid leukemia; ex vivo sensitivity test; STAT3
• ISSN: 2754-3242; 2754-1304; 2754-1304
• DOI: 10.3892/mi.2022.32

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 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.