^
    1m
    A Study to Assess the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of CC-90010 in Subjects With Advanced Solid Tumors and Relapsed/Refractory Non-Hodgkin's Lymphomas (clinicaltrials.gov)
    P1, N=139, Terminated, Celgene | Active, not recruiting --> Terminated; Business objectives have changed
    Trial termination • Metastases
    |
    trotabresib (BMS-986378)
    1m
    Study of the Bromodomain (BRD) and Extra-Terminal Domain (BET) Inhibitors BMS-986158 and BMS-986378 in Pediatric Cancer (clinicaltrials.gov)
    P1, N=41, Completed, Dana-Farber Cancer Institute | Active, not recruiting --> Completed
    Trial completion
    |
    MYC (V-myc avian myelocytomatosis viral oncogene homolog) • MYCN (MYCN Proto-Oncogene BHLH Transcription Factor) • BRD4 (Bromodomain Containing 4) • BRD3 (Bromodomain Containing 3)
    |
    MYCN amplification
    |
    ezobresib (BMS-986158) • trotabresib (BMS-986378)
    2ms
    A Study to Assess the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of CC-90010 in Subjects With Advanced Solid Tumors and Relapsed/Refractory Non-Hodgkin's Lymphomas (clinicaltrials.gov)
    P1, N=139, Active, not recruiting, Celgene | Trial completion date: Jun 2026 --> Sep 2024
    Trial completion date • Metastases
    |
    trotabresib (BMS-986378)
    4ms
    Study of the Bromodomain (BRD) and Extra-Terminal Domain (BET) Inhibitors BMS-986158 and BMS-986378 in Pediatric Cancer (clinicaltrials.gov)
    P1, N=41, Active, not recruiting, Dana-Farber Cancer Institute | Trial primary completion date: Jul 2024 --> Mar 2024
    Trial primary completion date
    |
    MYC (V-myc avian myelocytomatosis viral oncogene homolog) • MYCN (MYCN Proto-Oncogene BHLH Transcription Factor) • BRD4 (Bromodomain Containing 4) • BRD3 (Bromodomain Containing 3)
    |
    ezobresib (BMS-986158) • trotabresib (BMS-986378)
    4ms
    A Study of CC-90010 in Combination With Temozolomide With or Without Radiation Therapy in Participants With Newly Diagnosed Glioblastoma (clinicaltrials.gov)
    P1, N=184, Terminated, Celgene | Trial completion date: May 2026 --> Jul 2024 | Active, not recruiting --> Terminated; Business objectives have changed
    Trial completion date • Trial termination • Combination therapy
    |
    MGMT (6-O-methylguanine-DNA methyltransferase)
    |
    temozolomide • trotabresib (BMS-986378)
    4ms
    CNS Penetration, PK and PD of Preoperative CC-90010 in Progressive/Recurrent Diffuse Astrocytoma, Anaplastic Astrocytoma and Glioblastoma (clinicaltrials.gov)
    P1, N=20, Terminated, Celgene | Completed --> Terminated; Business objectives have changed.
    Trial termination
    |
    trotabresib (BMS-986378)
    5ms
    CNS Penetration, PK and PD of Preoperative CC-90010 in Progressive/Recurrent Diffuse Astrocytoma, Anaplastic Astrocytoma and Glioblastoma (clinicaltrials.gov)
    P1, N=20, Completed, Celgene | Active, not recruiting --> Completed
    Trial completion
    |
    trotabresib (BMS-986378)
    7ms
    A Study of Absorption, Metabolism, and Elimination CC-90010 in Participants With Advanced Solid Tumors (clinicaltrials.gov)
    P1, N=0, Withdrawn, Bristol-Myers Squibb | Not yet recruiting --> Withdrawn
    Trial withdrawal • Metastases
    |
    trotabresib (BMS-986378)
    8ms
    Trotabresib in Combination With Vinorelbine and Radiation Therapy for the Treatment of HER2+ Breast Cancer With Central Nervous System or Leptomeningeal Metastasis (clinicaltrials.gov)
    P1, N=0, Withdrawn, Northwestern University | N=34 --> 0 | Trial completion date: Dec 2031 --> Mar 2024 | Initiation date: Dec 2024 --> Dec 2023 | Not yet recruiting --> Withdrawn | Trial primary completion date: Dec 2029 --> Mar 2024
    Enrollment change • Trial completion date • Trial initiation date • Trial withdrawal • Trial primary completion date • Combination therapy
    |
    vinorelbine tartrate • trotabresib (BMS-986378)
    8ms
    Trotabresib in Combination With Vinorelbine and Radiation Therapy for the Treatment of HER2+ Breast Cancer With Central Nervous System or Leptomeningeal Metastasis (clinicaltrials.gov)
    P1, N=34, Not yet recruiting, Northwestern University | Initiation date: Dec 2023 --> Dec 2024
    Trial initiation date • Combination therapy
    |
    vinorelbine tartrate • trotabresib (BMS-986378)
    8ms
    Study of the Bromodomain (BRD) and Extra-Terminal Domain (BET) Inhibitors BMS-986158 and BMS-986378 in Pediatric Cancer (clinicaltrials.gov)
    P1, N=41, Active, not recruiting, Dana-Farber Cancer Institute | Recruiting --> Active, not recruiting | N=66 --> 41 | Trial completion date: Jun 2025 --> Jul 2024
    Enrollment closed • Enrollment change • Trial completion date
    |
    MYC (V-myc avian myelocytomatosis viral oncogene homolog) • MYCN (MYCN Proto-Oncogene BHLH Transcription Factor) • BRD4 (Bromodomain Containing 4) • BRD3 (Bromodomain Containing 3)
    |
    MYCN amplification
    |
    ezobresib (BMS-986158) • trotabresib (BMS-986378)
    10ms
    A Study to Assess the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of CC-90010 in Subjects With Advanced Solid Tumors and Relapsed/Refractory Non-Hodgkin's Lymphomas (clinicaltrials.gov)
    P1, N=139, Active, not recruiting, Celgene | Trial completion date: Apr 2024 --> Mar 2026 | Trial primary completion date: Oct 2023 --> Mar 2024
    Trial completion date • Trial primary completion date • Metastases
    |
    trotabresib (BMS-986378)
    11ms
    CNS Penetration, PK and PD of Preoperative CC-90010 in Progressive/Recurrent Diffuse Astrocytoma, Anaplastic Astrocytoma and Glioblastoma (clinicaltrials.gov)
    P1, N=20, Active, not recruiting, Celgene | Trial completion date: Aug 2023 --> Feb 2024
    Trial completion date
    |
    trotabresib (BMS-986378)
    12ms
    Trotabresib in Combination With Vinorelbine and Radiation Therapy for the Treatment of HER2+ Breast Cancer With Central Nervous System or Leptomeningeal Metastasis (clinicaltrials.gov)
    P1, N=34, Not yet recruiting, Northwestern University
    New P1 trial • Combination therapy
    |
    vinorelbine tartrate • trotabresib (BMS-986378)
    1year
    A Study of CC-90010 in Combination With Temozolomide With or Without Radiation Therapy in Participants With Newly Diagnosed Glioblastoma (clinicaltrials.gov)
    P1, N=194, Active, not recruiting, Celgene | Phase classification: P1b --> P1 | Trial completion date: Mar 2025 --> May 2026 | Trial primary completion date: Sep 2023 --> May 2024
    Phase classification • Trial completion date • Trial primary completion date • Combination therapy
    |
    MGMT (6-O-methylguanine-DNA methyltransferase)
    |
    RAS wild-type • IDH wild-type
    |
    temozolomide • trotabresib (BMS-986378)
    over1year
    Study of the Bromodomain (BRD) and Extra-Terminal Domain (BET) Inhibitors BMS-986158 and BMS-986378 in Pediatric Cancer (clinicaltrials.gov)
    P1, N=66, Recruiting, Dana-Farber Cancer Institute | Trial completion date: Dec 2024 --> Jun 2025 | Trial primary completion date: Dec 2023 --> Jun 2024
    Trial completion date • Trial primary completion date
    |
    MYC (V-myc avian myelocytomatosis viral oncogene homolog) • MYCN (MYCN Proto-Oncogene BHLH Transcription Factor) • BRD4 (Bromodomain Containing 4) • BRD3 (Bromodomain Containing 3)
    |
    MYCN amplification
    |
    ezobresib (BMS-986158) • trotabresib (BMS-986378)
    over1year
    CNS Penetration, PK and PD of Preoperative CC-90010 in Progressive/Recurrent Diffuse Astrocytoma, Anaplastic Astrocytoma and Glioblastoma (clinicaltrials.gov)
    P1, N=20, Active, not recruiting, Celgene | Trial completion date: Mar 2023 --> Aug 2023 | Trial primary completion date: Mar 2023 --> Aug 2023
    Trial completion date • Trial primary completion date
    |
    trotabresib (BMS-986378)
    over1year
    BRD4: New Hope in the Battle Against Glioblastoma. (PubMed, Pharmacol Res)
    In addition, several BRD4 inhibitors have been evaluated for therapeutic purposes as monotherapy or in combination with chemotherapy, radiotherapy, and immune therapies. Here, we provide a critical appraisal of studies evaluating various BRD4 inhibitors and degraders as novel treatment strategies against GBM.
    Review • Journal
    |
    BRD4 (Bromodomain Containing 4) • BRD2 (Bromodomain Containing 2) • BRD3 (Bromodomain Containing 3)
    |
    everolimus • temozolomide • lapatinib • doxorubicin hydrochloride • JQ-1 • Farydak (panobinostat) • birabresib (OTX015) • alisertib (MLN8237) • I-BET151 • ARV-825 • trotabresib (BMS-986378)
    over1year
    A Study of CC-90010 in Combination With Temozolomide With or Without Radiation Therapy in Participants With Newly Diagnosed Glioblastoma (clinicaltrials.gov)
    P1b, N=194, Active, not recruiting, Celgene | Recruiting --> Active, not recruiting
    Enrollment closed
    |
    MGMT (6-O-methylguanine-DNA methyltransferase)
    |
    RAS wild-type • IDH wild-type
    |
    temozolomide • trotabresib (BMS-986378)
    almost2years
    Study of the Bromodomain (BRD) and Extra-Terminal Domain (BET) Inhibitors BMS-986158 and BMS-986378 in Pediatric Cancer (clinicaltrials.gov)
    P1, N=66, Recruiting, Dana-Farber Cancer Institute | Trial completion date: Jul 2024 --> Dec 2024 | Trial primary completion date: Jul 2023 --> Dec 2023
    Trial completion date • Trial primary completion date
    |
    MYC (V-myc avian myelocytomatosis viral oncogene homolog) • MYCN (MYCN Proto-Oncogene BHLH Transcription Factor) • BRD4 (Bromodomain Containing 4) • BRD3 (Bromodomain Containing 3)
    |
    MYCN amplification
    |
    ezobresib (BMS-986158) • trotabresib (BMS-986378)
    2years
    A Study of CC-90010 in Combination With Temozolomide With or Without Radiation Therapy in Participants With Newly Diagnosed Glioblastoma (clinicaltrials.gov)
    P1b, N=194, Recruiting, Celgene | Trial completion date: Nov 2024 --> Mar 2025
    Trial completion date • Combination therapy
    |
    MGMT (6-O-methylguanine-DNA methyltransferase)
    |
    RAS wild-type • IDH wild-type
    |
    temozolomide • trotabresib (BMS-986378)
    almost3years
    A Study of CC-90010 in Combination With Temozolomide With or Without Radiation Therapy in Participants With Newly Diagnosed Glioblastoma (clinicaltrials.gov)
    P1b, N=194, Recruiting, Celgene | N=126 --> 194 | Trial primary completion date: Apr 2023 --> Aug 2023
    Enrollment change • Trial primary completion date • Combination therapy
    |
    MGMT (6-O-methylguanine-DNA methyltransferase)
    |
    RAS wild-type • IDH wild-type
    |
    temozolomide • trotabresib (BMS-986378)
    almost3years
    Study of the Bromodomain (BRD) and Extra-Terminal Domain (BET) Inhibitors BMS-986158 and BMS-986378 in Pediatric Cancer (clinicaltrials.gov)
    P1, N=66, Recruiting, Dana-Farber Cancer Institute | N=34 --> 66 | Trial primary completion date: Jul 2022 --> Jul 2023
    Enrollment change • Trial primary completion date
    |
    MYC (V-myc avian myelocytomatosis viral oncogene homolog) • MYCN (MYCN Proto-Oncogene BHLH Transcription Factor) • BRD4 (Bromodomain Containing 4) • BRD3 (Bromodomain Containing 3)
    |
    MYCN amplification
    |
    ezobresib (BMS-986158) • trotabresib (BMS-986378)
    almost3years
    Trotabresib (CC-90010, BMS-986378), a reversible, potent oral bromodomain and extraterminal inhibitor (BETi) in patients with high-grade gliomas: a phase 1 open-label ‘window of opportunity’ study (SNO 2021)
    Overall, trotabresib showed good tumor tissue penetration, with PD signals of response, and was well tolerated. A study of trotabresib + temozolomide in first-line glioblastoma is ongoing (NCT04324840).
    Clinical • P1 data
    |
    HEXIM1 (HEXIM P-TEFb Complex Subunit 1)
    |
    temozolomide • trotabresib (BMS-986378)
    over3years
    Bromodomain and extra-terminal inhibitors-A consensus prioritisation after the Paediatric Strategy Forum for medicinal product development of epigenetic modifiers in children-ACCELERATE. (PubMed, Eur J Cancer)
    Beyond NUT carcinoma, it was proposed that further clinical development of other pan-BET inhibitors in children should await the results of the first paediatric clinical trial of BMS-986158, unless there is compelling rationale based on the specific agent of interest. BDII-selective inhibitors, central nervous system-penetrant BET inhibitors (e.g. CC-90010), and those dual-targeting BET/p300 bromodomain are of particular interest and warrant further pre-clinical investigation. This meeting emphasised the value of a coordinated and integrated strategy to drug development in paediatric oncology. A multi-stakeholder approach with multiple companies developing a consensus with academic investigators early in the development of a class of compounds, and then engaging regulatory agencies would improve efficiency, productivity, conserve resources and maximise potential benefit for children with cancer.
    Clinical • Review • Journal
    |
    MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
    |
    ezobresib (BMS-986158) • trotabresib (BMS-986378)
    almost4years
    CNS Penetration, PK and PD of Preoperative CC-90010 in Progressive/Recurrent Diffuse Astrocytoma, Anaplastic Astrocytoma and Glioblastoma (clinicaltrials.gov)
    N=10 --> 25
    Clinical • Enrollment change
    |
    ALB (Albumin)
    |
    trotabresib (BMS-986378)