Phase Ib Trial With Birabresib, a Small-Molecule Inhibitor of Bromodomain and Extraterminal Proteins, in Patients With Selected Advanced Solid Tumors.

Birabresid = OTX015 = MK-8628. This is an OncoEthix/Merck study on their early generation pan-BET inhibitor. They've published before on hematological malignancies. And there have been conference abstracts on other clinical studies of OTX015 and other pan-BET inhibitors in solid tumors. But this is the first peer-reviewed, published study on the use of a pan-BET inhibitor in solid tumors. It is based on this clinical trial:

A Dose-Finding Study of OTX105/MK-8628, a Small Molecule Inhibitor of the Bromodomain and Extra-Terminal (BET) Proteins, in Adults With Selected Advanced Solid Tumors (MK-8628-003)

They conclude that intermittent dosing is ineffective relative to everyday continuous dosing. Of their 46 patients, 26 had castrate resistant prostate cancer, 10 had NUT midline carcinoma, and 10 had non–small-cell lung cancer. They focus primarily on the NUT carcinoma results (9 evaluatable patients), in which they achieved either partial response (3/9) or stable disease (3/9) with continuous dosing (they didn't do intermittent dosing w/ NUT carcinoma). For CRPC (24 evaluatable patients), they did both continuous (9 patients) and intermittent dosing (15 patients). For intermittent dosing, 7 had disease progression and 8 had stable disease. For continous dosing, 2 had disease progression and 7 had stable disease. I think they decided to focus on NUT carcinoma because of the 3 partial responses; however, achieving stable disease is also admirable and in light of that they could have highlighted CRPC results more.

They don't call out Gilead or Zenith by name, but cite their ongoing combo trials with enzalutamide and/or abiraterone for CRPC in the discussion: "Ongoing combination studies of BET inhibitors with enzalutamide or abiraterone (ClinicalTrials.gov identifiers: NCT02607228 and NCT02711956) will clarify the potential for such a strategy." Since Zenith has claimed that they can dose every day, this sets Zenith up nicely. The rumored Zenith Phase 1 publication may be similarly structured as this OTX-015 Phase 1 publication. Hopefully with less side effects and more efficacy!

BearDownAZ