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Ref Type Journal Article
PMID (32240793)
Authors Moreno V, Sepulveda JM, Vieito M, Hernández-Guerrero T, Doger B, Saavedra O, Ferrero O, Sarmiento R, Arias M, De Alvaro J, Di Martino J, Zuraek M, Sanchez-Pérez T, Aronchik I, Filvaroff EH, Lamba M, Hanna B, Nikolova Z, Braña I
Title Phase I study of CC-90010, a reversible, oral BET inhibitor in patients with advanced solid tumors and relapsed/refractory non-Hodgkin's lymphoma.
Journal Annals of oncology : official journal of the European Society for Medical Oncology
Vol
Issue
Date 2020 Mar 30
URL
Abstract Text Bromodomain and extra-terminal (BET) proteins are epigenetic readers that regulate expression of genes involved in oncogenesis. CC-90010 is a novel, oral, reversible, small-molecule BET inhibitor.CC-90010-ST-001 (NCT03220347; 2015-004371-79) is a phase I dose-escalation and expansion study of CC-90010 in patients with advanced or unresectable solid tumors and relapsed/refractory (R/R) non-Hodgkin's lymphoma (NHL). We report results from the dose escalation phase, which explored 11 dose levels and four dosing schedules, two weekly (2 days on/5 days off; 3 days on/4 days off), one biweekly (3 days on/11 days off), and one monthly (4 days on/24 days off). The primary objectives were to determine the safety, maximum tolerated dose (MTD) and/or recommended phase II dose (RP2D) and schedule. Secondary objectives were to evaluate signals of early antitumor activity, pharmacokinetics, and pharmacodynamics.This study enrolled 69 patients, 67 with solid tumors and two with diffuse large B-cell lymphoma (DLBCL). The median age was 57 years (range, 21-80) and the median number of prior regimens was four (range, 1-9). Treatment-related adverse events (TRAEs) were mostly mild and manageable; grade 3/4 TRAEs reported in more than two patients were thrombocytopenia (13%), anemia, and fatigue (4% each). Six patients had dose-limiting toxicities. MTDs were 15 mg (2 days on/5 days off), 30 mg (3 days on/11 days off), and 45 mg (4 days on/24 days off). The RP2D and schedule selected for expansion was 45 mg (4 days on/24 days off). As of 8 October 2019, one patient with grade 2 astrocytoma achieved a complete response, one patient with endometrial carcinoma had a partial response, and six patients had prolonged stable disease ≥11 months.CC-90010 is well tolerated, with single-agent activity in patients with heavily pretreated, advanced solid tumors.

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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
Drug Name Trade Name Synonyms Drug Classes Drug Description
CC-90010 CC 90010|CC90010|BET Inhibitor CC-90010 BET Inhibitor (Pan) 27 CC-90010 is a reversible, small molecule drug that binds to BD2 (bromodomain 2) of BET proteins and inhibits interaction with acetylated histones, potentially resulting in disrupted expression of genes that promote cell growth, and inhibition of proliferation of tumor cells overexpressing BET proteins (PMID: 32240793).
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
Unknown unknown non-Hodgkin lymphoma not applicable CC-90010 Phase I Actionable In a Phase I trial, CC-90010 treatment demonstrated safety, and resulted in an overall response rate of 2.9% (2/69, 1 complete response, 1 partial response), stable disease in 33.3% (23/69), and a median progression-free survival of 1.9 months in patients with advanced solid tumors or relapsed/refractory non-Hodgkin lymphoma (PMID: 32240793; NCT03220347). 32240793
Unknown unknown endometrial carcinoma not applicable CC-90010 Case Reports/Case Series Actionable In a Phase I trial, CC-90010 treatment demonstrated safety, and resulted in a partial response in an endometrial carcinoma patient harboring an ESR1-AKAP12 fusion, ESR1 amplification, and PIK3CA and FGFR2 mutations (PMID: 32240793; NCT03220347). 32240793
Unknown unknown thymic carcinoma not applicable CC-90010 Case Reports/Case Series Actionable In a Phase I trial, CC-90010 treatment demonstrated safety, and resulted in a 17% tumor reduction in a patient with metastatic malignant thymoma (PMID: 32240793; NCT03220347). 32240793
Unknown unknown fibrillary astrocytoma not applicable CC-90010 Case Reports/Case Series Actionable In a Phase I trial, CC-90010 treatment demonstrated safety, and resulted in a complete response in a patient with IDH-mutant diffuse astrocytoma with MGMT methylation (PMID: 32240793; NCT03220347). 32240793
Unknown unknown Advanced Solid Tumor not applicable CC-90010 Phase I Actionable In a Phase I trial, CC-90010 treatment demonstrated safety, and resulted in an overall response rate of 2.9% (2/69, 1 complete response, 1 partial response), stable disease in 33.3% (23/69), and a median progression-free survival of 1.9 months in patients with advanced solid tumors or relapsed/refractory non-Hodgkin lymphoma (PMID: 32240793; NCT03220347). 32240793