trotabresib (BMS-986378) / BMS - LARVOL DELTA

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

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

Metastases • Trial termination • 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

Metastases • Trial completion date • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • 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 | 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

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

Metastases • Trial completion date • Trial primary completion date • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • 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 | 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

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 | Sponsor: Celgene | Phase classification: P1b ➔ P1 | Trial completion date: Mar 2025 ➔ May 2026 | Trial primary completion date: Sep 2023 ➔ May 2024

Combination therapy • Phase classification • Trial completion date • Trial primary completion date • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor • MGMT

Trotabresib (CC-90010) combined with concomitant temozolomide (TMZ) plus radiotherapy (RT) and adjuvant TMZ in patients (pts) with newly diagnosed primary glioblastoma (ndGBM): Updated results from a phase Ib/II study (ESMO 2023) - P1b | "30 mg/day is the recommended phase 2 dose. NE, not estimable; OS, overall survival; PFS, progression-free survival."

Clinical • P1/2 data • Brain Cancer • CNS Tumor • Glioblastoma • 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=66 | Recruiting | Sponsor: 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 • 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: Mar 2023 ➔ Aug 2023 | Trial primary completion date: Mar 2023 ➔ Aug 2023

Trial completion date • Trial primary completion date • Anaplastic Astrocytoma • Astrocytoma • Brain Cancer • CNS Tumor • Glioblastoma • 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

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."

Journal • Review • Brain Cancer • CNS Tumor • Glioblastoma • Glioma • Oncology • Solid Tumor • BRD2 • BRD3 • BRD4

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 | Sponsor: Celgene | Recruiting ➔ Active, not recruiting

Enrollment closed • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor • MGMT

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

Metastases • Trial completion date • Trial primary completion date • 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 (Nature) - P1 | N=139 | NCT03220347 | Sponsor: Bristol-Myers Squibb | "Here, we report long-term follow-up results from part A (N = 69) and data from patients treated with the RP2D of 45 mg/day 4 days on/24 days off or an alternate RP2D of 30 mg/day 3 days on/11 days off in the dose-expansion cohorts (parts B [N = 25] and C [N = 41]). Treatment-related adverse events (TRAEs) are reported in almost all patients. The most common severe TRAEs are hematological. Toxicities are generally manageable, allowing some patients to remain on treatment for ≥2 years, with two patients receiving ≥3 years of treatment. 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)."

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

Trotabresib (CC-90010) in combination with concomitant temozolomide plus radiotherapy and adjuvant temozolomide in patients with newly diagnosed glioblastoma: updated results from a phase 1b/2 study (SNO 2022) - P1b | "Key objectives are to compare progression-free and overall survival, safety, and tolerability. Longer follow-up from part A and the first disclosure of data from part B will be presented."

Clinical • Combination therapy • P1/2 data • Brain Cancer • Glioblastoma • Hematological Disorders • Oncology • Solid Tumor • Thrombocytopenia