Skip to main content
editorial
. 2019 Nov 6;4(2):pkz092. doi: 10.1093/jncics/pkz092

Table 1.

Clinical trials evaluating BET inhibitors with results in patients with solid tumors*

Clinical trial Design Drug Patients, No. Overall response rate Median time of study Toxicity Recommended dose Publication
NCT01949883 3 + 3, escalation CPI-0610

  • 64 lymphoma pts

  • DLBCL n = 36 (56%)

  • FL n = 8 (12.5%)

  • HL n = 5 (8%)

  • MCL n = 3 (5%)

  • Other n = 12 (19%)

  • 38 evaluable pts

  • CR 2 pts

  • PR 3 pts

  • SD 17 pts

 NA

  • G3

  • rash n = 1

  • Neutropenia n = 1

  • Diarrhea n=2

  • G4 thrombocytopenia n = 3

 Safety and PK data, 225 mg TAT 2018, (23)
NCT02259114 3 + 3, escalation MK-862 (birabresib)

  • 46 pts

  • NUT n = 10 (22%)

  • CRPC n = 26 (57%)

  • NSCLC n = 10 (22%)

  • 42 evaluable pts

  • CR 0

  • PR 3 NMC pts (7%)

  • SD n = 25 (60%)

  • NMC n = 3

  • CRPC n = 15

  • NSCLC n = 7

  • 2.3 m (0.2–15.4 m)

  • PR (NMC), 1.4–8.4 m, 1 after 10 m

  • SD

  • CRPC n = 2: 3.5 m, 7.8 m

  • NSCLC n

  • G3–4

  • nausea n = 1

  • vomiting n = 1

  • fatigue n = 2

  • anemia n = 11

  • thrombocytopenia n = 20

  • ALT n = 2

  • Acute kidney injury n = 1

  • Thrombocytopenia nadir

  • 32 d (range = 12–211)

 PK data, 80 mg Lewin 2018 (9)
NCT02683395 3 + 3, escalation PLX51107

  • 36 pts

  • Uveal melanoma n = 11

  • Sarcoma n = 6

  • NSCLC n = 2

  • Breast n = 2

  • CRPC n = 2

  • 36 evaluable pts

  • SD n = 8

  • Uveal Melanoma n = 2

  • Sarcoma n = 3

  • NSCLC n = 1

  • CRPC n = 1

 4–14 mo

  • G3

  • Nausea n = 1

  • Thrombocytopenia n = 1

 Preclinical toxicology data Patnaik et al, JCO 2018 (23)
NCT02391480 3 + 3, escalation ABBV-075

  • 72 pts

  • Uveal Melanoma n = 10

  • Breast n = 8

  • Pancreatic n = 6

  • HNSCC n = 5

  • CRPC n = 3

  • Others n = 40

  • 65 evaluable pts

  • SD n = 25 (39%)

  • PD n = 40 (61%)

 7.6 w (range = 0.9–39.6 wk)

  • G3–4

  • Thrombocytopenia n = 16

  • Anemia n = 8

 Safety Piha P. et al, 2019 (24)
NCT02711137 3 + 3, escalation INCB057643

  • 16 pts

  • Solid tumors N = 13

  • Lymphoma (FL) N = 3

  • 11 evaluable pts

  • PR n = 1 lymphoma (8 m)

  • SD Biliary Cancer n = 1 >6 m; Solid tumor n = 4 <6 m

  • PD 6 pts

 59.5 d (range = 6–282) d

  • G3–4

  • Thrombocytopenia n = 2 (13%)

  • Anemia n = 1 (6%)

  • Bilirubin n = 1 (6%)

  • Hyperglycemia n = 1 (6%)

  • INR n = 1 (6%)

 DLTs during cycle 1 Falchook G. et al, 2019 (25)
NCT02516553

  • Bayesian logistic regression model

  • Arm A: continuous regimen

  • Arm B: 14 d on/7 d off

 BI 894999

  • 46 pts

  • Arm A n = 21

  • Arm B n = 16

  • 36 evaluable pts

  • PR n = 2 (6%) small bowel & esophageal SCC

  • SD 14 (39%)

  • n =2 ≥ 4 cycles

  • 2 cycles (range, 1–14)

  • PR

  • 1 pt cycle 2–14

  • 1 pt cycle 2–8

  • G3–4

  • Thrombocytopenia n = 24 (65%)

  • Fatigue n = 3

  • Diarrhea n = 5

 Safety DLT, MTD Bechter O. et al, 2018 (26)
NCT02419417

  • 3 schedules: A (5 d on/2 d off)

  • B (14 d on/7 d off)

  • C (7 d on/14 d off)

 BMS 986158

  • 75 pts

  • NUT n = 4

  • Other solid tumor

 1 pt NUT (schedule A) 279 d, SD -16% 1 pt with SD, 279 d (9.3 months)

  • G3–4

  • Thrombocytopenia n = 10 (15%)

  • Fatigue n =1 (1%)

  • Nausea 1 pt (1%)

 Safety and PK data Hilton J. et al, 2018 (27)
NCT02369029 Adaptive design:

  1. dose escalation MTD - solid tumors

  2. expansion at MTD solid dose level

  3. dose escalation in hematologic + expansion at MTD hematologic

 BAY 17437

  • 8 pts

  • Terminated because of toxicity

  • CRC n = 3

  • NET n = 1

  • Ovarian n = 1

  • CRPC n =1

  • Thyroid n = 1

  • Rectal NET n = 1

 8 pts SD n = 2 pts, 6 cycles NA

  • G3-4

  • Headache n = 3

  • Vomiting n = 2 (25%)

 Safety and PK data Postel-Vinay S. et al, 2018 (28)
NCT01587703 3 + 3, escalation GSK525762

  • 65 pts

  • CRC n = 22

  • NMC n = 11

  • CRPC n = 9

  • SCLC n = 6

  • Breast n = 5

  • NSCLC n = 2

  • Neuroblast n = 1

  • Myeloblast n = 1

  • NC cohort n = 19

  • PR n = 2 (11%)

  • SD n = 8

  • Non-NMC n = 41

  • uPR Breast n = 1

  • SD > 4 m CRPC, CRC

 NMC median PFS 2.5 m

  • G3–4

  • Thrombocytopenia n = 24

  • Nausea n = 2

  • Anorexia n = 3

  • Vomiting n = 1

  • Anemia n = 5

  • Br n = 3

  • Fatigue n = 3

 Safety and PK data Piha-Paul S. et al, 2018 (8)

*CRC = colorectal cancer; CRPC = castration-resistant prostate cancer; DLBCL, n = 36 (56%); DLT = dose-limiting toxicity; ENA = EORTC-NCI-AACR; FL = follicular lymphoma; HL = Hodgkin lymphoma; HNSCC = Head and Neck Squamous Cell Carcinoma; MCL = mantle cell lymphoma; MTD = maximum tolerated dose; NET = neuroendocrine tumor; NMC = NUT–midline carcinoma; NSCLC = Non-Small Cell Lung Cancer; PK = pharmacokinetics; pts = patients; PR = partial response; SCLC = Small Cell Lung Cancer; SD = stable disease; uPR = unconfirmed partial response.