Early Research on Birabresib in Prostate Cancer and Other Solid Tumors
Posted: Monday, November 26, 2018
In a phase Ib trial, Christophe Massard, MD, PhD, of the Institut Gustave Roussy, Villejuif, France, and colleagues found that the first-in-class drug birabresib (MK8628/OTX015), a bromodomain inhibitor, has dose proportional exposure, rapid absorption, and a favorable toxicity profile. In fact, clinical activity was reported for a select patient population. For future phase II testing in solid tumors, the authors a dose of 80 mg once a day with continuous dosing. These results were published in the Journal of Clinical Oncology.
In this multicenter, nonrandomized, open-label trial, 46 patients with various tumor types received birabresib. A total of 26 patients had castration-resistant prostate cancer, in addition, 10 patients had non–small cell lung cancer and 10 patients had nuclear protein in testis midline carcinoma. They were started at 80 mg once daily continuously (cohort A) or 100 mg for 7 consecutive days (cohort B) in 21-day cycles with parallel dose escalation. Patients received a median of three 21-day cycles.
Dose limiting toxicities occurred in 21% of evaluable patients in cohort A and in two-thirds of patients in cohort B. No dose-limiting toxicities were observed for patients in cohort B. Of the 24 patients who had prostate cancer and were evaluable for response, 15 had stable disease, and 9 had disease progression. In total, 83% of patients had treatment-related adverse events, the most common being diarrhea (37%), nausea, (37%), anorexia (30%), vomiting, (26%), and thrombocytopenia (22%).
“Future evaluations of birabresib need to consider intermittent scheduling to mitigate the potential toxicities of continuous dosing,” the authors concluded.