Reference Detail

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	Vol	Issue	Date	Pages	Journal Short Title
Annals of oncology : official journal of the European Society for Medical Oncology			2020 Mar 30	780-788	Ann Oncol

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
CC-90010	CC-90010	0	3

Drug Name	Trade Name	Synonyms	Drug Classes	Drug Description
CC-90010		CC 90010\|CC90010\|BMS-986378\|BMS 986378\|BMS986378	BET Inhibitor (Pan) 32	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