Phase I study of CC-90010, a reversible, oral BET inhibitor in patients with advanced solid tumors and relapsed/refractory non-Hodgkin's lymphoma.
Ann Oncol
; 31(6): 780-788, 2020 06.
Article
en En
| MEDLINE
| ID: mdl-32240793
ABSTRACT
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 ANDMETHODS:
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.Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Linfoma no Hodgkin
/
Linfoma de Células B Grandes Difuso
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Antineoplásicos
Límite:
Adult
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Aged
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Aged80
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Humans
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Middle aged
Idioma:
En
Revista:
Ann Oncol
Asunto de la revista:
NEOPLASIAS
Año:
2020
Tipo del documento:
Article