Investigational Bromodomain Inhibitor Shows Clinical Activity in Some Blood Cancers
The results from a phase I study of a new investigational epigenetic therapy called OTX015, a small-molecule inhibitor that blocks the activity of bromodomain and extraterminal (BET)-bromodomain proteins, is showing clinical activity in some blood cancers, including leukemia and lymphoma. The study was presented at the American Association for Cancer Research (AACR) Annual Meeting 2014 in San Diego.
Study Methods and Findings
The clinical trial was designed to determine the recommended dose and pharmacokinetics of oral OTX015 as a single agent. The study included 42 patients with a median age of 70 years and a median of two prior therapies. Of the 42 patients, 21 had acute leukemia, mainly acute myelogenous leukemia (AML), and 21 had a variety of other hematologic malignancies, including diffuse large B-cell lymphoma and multiple myeloma.
The patients were assigned to a single dose of 10 mg, 40 mg, or 80 mg of OTX015 daily, or to two 40-mg doses of the therapy daily. There were three to six patients with acute leukemia and three to six patients with another blood cancer assigned to each dosing regimen.
Outcomes
Clinically meaningful activity was observed in 7 of the 38 patients for whom data were mature enough to evaluate. Four of these seven patients received a single dose of 80 mg of OTX015 daily, one received 10 mg daily, and the other two patients received 40 mg daily. Responses occurred in patients with various clinical, cytogenetic, and molecular profiles. Treatment of three of these seven patients is ongoing.
Among the patients who benefited clinically are four with AML. One has had an ongoing complete response, and a second patient is experiencing a complete response with incomplete recovery, meaning there are no leukemia cells detectable in the bone marrow and blood, but only a partial recovery of normal blood cells. Two other patients with AML had a significant decrease in the number of leukemia cells in their bone marrow and blood. Partial responses were seen in two lymphoma patients, one with diffuse large B-cell lymphoma and one with lymphoplasmacytic lymphoma. One patient with follicular lymphoma has an ongoing minor response with clinical symptom clearance.
No dose-limiting toxicities have been observed yet in patients with leukemia, but thrombocytopenia is emerging as a dose-limiting toxicity for patients with other hematologic malignancies. Other sporadic adverse events reported include increased blood glucose in previously diabetic patients, mild to moderate digestive symptoms, and a drop in platelet counts.
Enrollment into the trial is ongoing, with patients assigned to single doses of 120 mg of OTX015 daily.
“With dose escalation still ongoing, we have yet to determine the optimal dosing and schedule for monotherapy with OTX015,” Esteban Cvitkovic, MD, a coauthor of the study and Chief Scientific Officer of OncoEthix, said in a statement. “Given that, we are very pleased to have already seen clear evidence of antineoplastic activity.”
The study was funded by OncoEthix. Dr. Cvitkovic is the founder and Chief Scientific Officer of OncoEthix.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
