Sistema de Salut de Catalunya
Institut Català de la Salut
[Moreno V, Hernández-Guerrero T, Doger B] START Madrid-FJD, Hospital Fundación Jimenez Diaz, Madrid, Spain. [Sepulveda JM] Department of Medical Oncology, Hospital Universitario 12 de Octubre, Madrid, Spain. [Vieito M, Saavedra O, Braña I] Department of Gene Expression and Cancer, Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain
Vall d'Hebron Barcelona Hospital Campus
2021-09-16T08:55:34Z
2021-09-16T08:55:34Z
2020-06
Inhibidor de BET; Limfoma no Hodgkin; Tumors sòlids
Inhibidor de BET; Linfoma no Hodgkin; Tumores sólidos
BET inhibitor; Non-Hodgkin's lymphoma; Solid tumors
Background 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. Patients and methods 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. Results 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. Conclusions CC-90010 is well tolerated, with single-agent activity in patients with heavily pretreated, advanced solid tumors.
This work was supported by Celgene Corporation, Summit, NJ, USA. (no grant number).
Article
Published version
English
Hodgkin, Malaltia de - Tractament; DISEASES::Neoplasms::Neoplasms by Histologic Type::Lymphoma::Lymphoma, Non-Hodgkin; Other subheadings::Other subheadings::Other subheadings::/drug therapy; ENFERMEDADES::neoplasias::neoplasias por tipo histológico::linfoma::linfoma no Hodgkin; Otros calificadores::Otros calificadores::Otros calificadores::/farmacoterapia
Elsevier
Annals of Oncology;31(6)
https://doi.org/10.1016/j.annonc.2020.03.294
Attribution-NonCommercial-NoDerivatives 4.0 International
http://creativecommons.org/licenses/by-nc-nd/4.0/
