Table 3 BRD4 BD1 and BD2 bromodomain inhibitors in clinical trials.
From: Super-enhancers and the super-enhancer reader BRD4: tumorigenic factors and therapeutic targets
BRD4 inhibitor | Cancer type | Trial Phase | Anticancer effects | Side effects | References |
|---|---|---|---|---|---|
OTX015 | Lymphoma, myeloma & acute myeloid leukemia | Phase I | A minority of patients achieve complete or partial remission | Thrombocytopenia, diarrhea, vomiting, fatigue, and hyponatraemia. Manageable, progressed into Phase II trials. | |
CC-90010 alone, or CC-90010 + Temozolomide | Glioblastomaother solid tumors & lymphoma | Phase I & Ib | Anticancer effects in a minority of patients by CC-90010. Promising anticancer effects by combination therapy | Thrombocytopenia, anemia, and fatigue. Well-tolerated. | |
ABBV-075, ABBV-075 plus Venetoclax | Prostate cancer, other solid tumors, acute myeloid leukemia | Phase I | Monotherapy shows limited anticancer effects, ABBV-075 plus Venetoclax is much more effective. | Dysgeusia, loss of appetite, diarrhea, fatigue, nausea, thrombocytopenia, and anemia. Manageable. | |
INCB054329 or INCB057643 | Solid tumor & lymphoma | Phase I/II | A minority of patients achieve complete or partial remission. | Thrombocytopenia, nausea, fatigue and decreased appetite. Manageable. | [71] |
Pelabresib (CPI-0610) Plus Ruxolitinib | Myelofibrosis | Phase II & III | The majority of patients achieve partial response. | Thrombocytopenia and anemia. Well-tolerated. | |
GSK525762 (Molibresib) | NUT carcinoma, leukemia, lymphoma, myeloma | Phase I | A minority of patients achieve complete or partial remission. | Thrombocytopenia, anemia and neutropenia limit dose-escalation and anticancer effects | |
BAY 1238097 | Solid tumors | Phase I | On-target effects on BRD4-inhibition biomarkers, such as reduction in MYC expression. | Dose-limiting toxicities including nausea, vomiting, headache, back pain and fatigue. Trial was terminated. | [77] |
ODM-207 | Solid tumors including prostate cancer | Phase I | No complete or partial responses were observed | Thrombocytopenia, anorexia, nausea, diarrhea and fatigue, indicating a narrow therapeutic window | [78] |
