OPB-111077, a novel inhibitor of STAT3 and mitochondrial oxidative phosphorylation, showed some clinical activity, including 1 durable partial response in a patient with diffuse large B-cell lymphoma, in a cohort of patients with advanced cancer, according to a study published in The Oncologist.1

Preclinical evidence suggested that OPB-111077 might be a safe and efficacious drug among patients with advanced cancer for whom there are limited options. For this first in-human phase 1 study (ClinicalTrials.gov Identifier: NCT01711034), researchers evaluated the optimal dosage, safety, and efficacy of OPB-111077 in dose-escalation and dose expansion cohorts of patients with advanced cancer. The co-primary endpoints were safety and tolerability.

Eighteen and 127 patients were enrolled into the dose-escalation and dose expansion cohorts, respectively. Patients had one of a variety of cancers, including lymphoma, prostate cancer, ovarian cancer, lung cancer, multiple myeloma, and gastric cancer; the mean ages were 64.4 years and 60.9 years in the escalation and expansion cohorts, respectively. Most patients had received prior surgery and chemotherapy, and about half of patients in both cohorts had received prior radiotherapy.

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OPB-111077 was administered daily in 28-day cycles until disease progression. The maximum tolerated dose was defined at 250 mg QD; the most frequently reported treatment-related adverse events (AEs) were nausea, fatigue, and vomiting.

In the escalation and expansion stages, 60% and 32.3% of patients, respectively, had a best overall response of stable disease; 7 patients had stable disease for at least 8 treatment cycles. One patient with diffuse large B-cell lymphoma had an ongoing partial response.

No complete responses were observed.

While uncommon, serious AEs, including cardiac disorder (6%), respiratory AEs (8%), and infections/infestations (4%), were noted.

The authors concluded that “OPB-111077 can be administered safely…Although notable clinical activity was observed in a subject with diffuse large B-cell lymphoma, monotherapy demonstrated minimal clinical activity against unselected tumors overall.”


  1. Tolcher A, Flaherty K, Shapiro GI, et al. A first‐in‐human phase 1 study of OPB‐111077, a small‐molecule STAT3 and oxidative phosphorylation inhibitor, in patients with advanced cancers. Oncologist. 2018 Mar 6. doi: 10.1634/theoncologist.2017-0325 [Epub ahead of print]