trotabresib (BMS-986378) / BMS - LARVOL DELTA

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=100 | Not yet recruiting | Sponsor: Celgene

First-in-human • New P1 trial • B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Solid Tumor

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 | Sponsor: Celgene | Active, not recruiting ➔ Terminated; Business objectives have changed

First-in-human • Trial termination • B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Solid Tumor

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 | Sponsor: Celgene | Trial completion date: Nov 2023 ➔ Apr 2024 | Trial primary completion date: Apr 2023 ➔ Oct 2023

First-in-human • Trial completion date • Trial primary completion date • B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Solid Tumor

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=145 | Recruiting | Sponsor: Celgene | Trial completion date: Apr 2022 ➔ Aug 2023 | Trial primary completion date: May 2020 ➔ Aug 2021

First-in-human • Trial completion date • Trial primary completion date • B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

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 | Sponsor: Celgene | Trial completion date: Apr 2024 ➔ Mar 2026 | Trial primary completion date: Oct 2023 ➔ Mar 2024

First-in-human • Trial completion date • Trial primary completion date • B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Solid Tumor

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 | Recruiting | Sponsor: Celgene | Trial completion date: Aug 2023 ➔ Sep 2022 | Trial primary completion date: Aug 2021 ➔ Sep 2022

First-in-human • Trial completion date • Trial primary completion date • B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Solid Tumor

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 | Sponsor: Celgene | Trial completion date: Jun 2026 ➔ Sep 2024

First-in-human • Trial completion date • B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Solid Tumor

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 | Sponsor: Celgene | Trial completion date: Jun 2023 ➔ Nov 2023 | Trial primary completion date: Dec 2022 ➔ Apr 2023

First-in-human • Trial completion date • Trial primary completion date • B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Solid Tumor

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 | Sponsor: Celgene | Trial completion date: Dec 2022 ➔ Jun 2023

First-in-human • Trial completion date • B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Solid Tumor

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 | Sponsor: Celgene | Recruiting ➔ Active, not recruiting

Enrollment closed • First-in-human • B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Solid Tumor

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=115 | Recruiting | Sponsor: Celgene | Not yet recruiting ➔ Recruiting

Enrollment open • First-in-human • B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Solid Tumor

BET inhibitor trotabresib in heavily pretreated patients with solid tumors and diffuse large B-cell lymphomas. (PubMed, Nat Commun) - P1 | "CC-90010-ST-001 (NCT03220347) is an open-label phase I study of trotabresib, an oral BET inhibitor, in heavily pretreated patients with advanced solid tumors and relapsed/refractory diffuse large B-cell lymphoma (DLBCL). Trotabresib monotherapy shows antitumor activity, with an ORR of 13.0% (95% CI, 2.8-33.6) in patients with R/R DLBCL (part B) and an ORR of 0.0% (95% CI, 0.0-8.6) and a CBR of 31.7% (95% CI, 18.1-48.1) in patients with advanced solid tumors (part C). These results support further investigation of trotabresib in combination with other anticancer agents."

Journal • P1 data • Diffuse Large B Cell Lymphoma • Hematological Disorders • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Solid Tumor

Pd-catalyzed Miyaura borylations mediated by potassium pivalate with alcohol cosolvents (ACS-Fall 2025) - "Extensive studies into the identity and amount of the alcohol cosolvent were conducted to maximize the solubility of KOPiv while minimizing undesired reduction and homocoupling impurities. The improved protocol for Miyaura borylation was applied toward the synthetic sequence of bromodomain and extra-terminal (BET) inhibitor BMS-986378 on a decagram scale, leading to a 3-fold reduction of catalyst loading, replacement of an expensive, hygroscopic base (CsOAc), and a simplified procedure for product isolation."

Addiction (Opioid and Alcohol)

Anti-tumor effects following BET inhibition in preclinical models of pediatric and AYA osteosarcoma (AACR 2025) - "Effect of BETi (AZD5153, BMS-986378, ZEN-3694) in clinical trials for pediatric and adult solid tumors were investigated...To interrogate mechanisms of action, RNA-seq analysis of BET/BRD4 inhibition via AZD5153, PROTAC (ARV-825), and BRD4 siRNA in OS cell lines revealed distinct and overlapping patterns of alterations in gene expression...At the transcript level, increased DHRS2 was evident with no changes in TMPRSS9. These data sets reveal the promise of BETi for treatment of OS PDX derived from treatment naïve patients some of which go on to relapse, and in OS PDX derived from metastatic sites."

Preclinical • Oncology • Osteosarcoma • Sarcoma • Solid Tumor • BRD2 • BRD4 • DHRS2 • H2AX

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 | Sponsor: Dana-Farber Cancer Institute | Active, not recruiting ➔ Completed

Trial completion • Brain Cancer • Hematological Malignancies • Lymphoma • NUT Midline Carcinoma • Oncology • Pediatrics • Solid Tumor • BRD3 • BRD4 • MYC • MYCN

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 | Sponsor: Dana-Farber Cancer Institute | Trial primary completion date: Jul 2024 ➔ Mar 2024

Trial primary completion date • Brain Cancer • Hematological Malignancies • Lymphoma • NUT Midline Carcinoma • Oncology • Pediatrics • Solid Tumor • BRD3 • BRD4 • MYC • MYCN

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 | Sponsor: Celgene | Trial completion date: May 2026 ➔ Jul 2024 | Active, not recruiting ➔ Terminated; Business objectives have changed

Combination therapy • Trial completion date • Trial termination • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor • MGMT

CNS Penetration, PK and PD of Preoperative CC-90010 in Progressive/Recurrent Diffuse Astrocytoma, Anaplastic Astrocytoma and Glioblastoma (clinicaltrials.gov) - P1 | N=20 | Terminated | Sponsor: Celgene | Completed ➔ Terminated; Business objectives have changed.

Trial termination • Anaplastic Astrocytoma • Astrocytoma • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor

CNS Penetration, PK and PD of Preoperative CC-90010 in Progressive/Recurrent Diffuse Astrocytoma, Anaplastic Astrocytoma and Glioblastoma (clinicaltrials.gov) - P1 | N=20 | Completed | Sponsor: Celgene | Active, not recruiting ➔ Completed

Trial completion • Anaplastic Astrocytoma • Astrocytoma • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor

A Study of Absorption, Metabolism, and Elimination CC-90010 in Participants With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=0 | Withdrawn | Sponsor: Bristol-Myers Squibb | Not yet recruiting ➔ Withdrawn

Metastases • Trial withdrawal • Oncology • Solid Tumor

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 | Sponsor: 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

Combination therapy • Enrollment change • Trial completion date • Trial initiation date • Trial primary completion date • Trial withdrawal • Breast Cancer • CNS Tumor • HER2 Breast Cancer • Oncology • Solid Tumor

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 | Sponsor: Northwestern University | Initiation date: Dec 2023 ➔ Dec 2024

Combination therapy • Trial initiation date • Breast Cancer • CNS Tumor • HER2 Breast Cancer • Oncology • Solid Tumor

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 | Sponsor: Dana-Farber Cancer Institute | Recruiting ➔ Active, not recruiting | N=66 ➔ 41 | Trial completion date: Jun 2025 ➔ Jul 2024

Enrollment change • Enrollment closed • Trial completion date • Brain Cancer • Hematological Malignancies • Lymphoma • NUT Midline Carcinoma • Oncology • Pediatrics • Solid Tumor • BRD3 • BRD4 • MYC • MYCN

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 | Sponsor: Celgene | Trial completion date: Aug 2023 ➔ Feb 2024

Trial completion date • Anaplastic Astrocytoma • Astrocytoma • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor

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 | Sponsor: Northwestern University

Combination therapy • New P1 trial • Breast Cancer • CNS Tumor • HER2 Breast Cancer • Oncology • Solid Tumor