Lewin J, et al. - In this phase Ib study, researchers assessed the safety, efficacy, and pharmacokinetics of birabresib (a first-in-class bromodomain inhibitor with activity in select hematologic tumors) in patients with castrate-resistant prostate cancer, nuclear protein in testis midline carcinoma (NMC), and non–small-cell lung cancer. In patients with select solid tumors, 80 mg once daily with continuous dosing was noted to be the recommended phase II dose of birabresib. Birabresib showed a favorable safety profile and clinical activity in NMC, and it had dose-proportional exposure.

Methods

• This study included 47 patients, who were given birabresib once daily at starting doses of 80 mg continuously (cohort A) or 100 mg for 7 consecutive days (cohort B) in 21-day cycles using a parallel dose escalation 3 + 3 design.
• Determination of the occurrence of dose-limiting toxicities (DLTs) and the recommended phase II dose was the primary goal.

Results

• A total of 46 patients were treated; 26 had castrate-resistant prostate cancer, 10 NMC, and 10 non–small-cell lung cancer.
• Researchers found that for cohort A, DLTs were reported in four of 19 (21%) patients at 80 mg once daily (grade 3 thrombocytopenia [n = 3], ALT/hyperbilirubinemia [n = 1]) and two of three had DLTs at 100 mg once daily (grade 2 anorexia and nausea with treatment delay > 7 days [n = 1], grade 4 thrombocytopenia [n = 1]).
• For cohort B, no DLTs occurrence was found.
• Treatment-related adverse events were seen in 38 (83%) of 46 patients (diarrhea, 17 [37%]; nausea, 17 [37%]; anorexia, 14 [30%]; vomiting, 12 [26%]; thrombocytopenia 10 [22%]).
• A partial response (Response Evaluation Criteria in Solid Tumors [RECIST] version 1.1) with duration of 1.4 to 8.4 months was observed in three patients with NMC (80 mg once daily).
• A dose-proportional increase in birabresib exposure and rapid absorption was revealed in pharmacokinetic analysis.