Phase I Study of Entinostat, Atezolizumab, Carboplatin, and Etoposide in Previously Untreated Extensive-Stage Small Cell Lung Cancer, ETCTN 10399.
Oncologist
; 28(11): 1007-e1107, 2023 Nov 02.
Article
em En
| MEDLINE
| ID: mdl-37555284
ABSTRACT
BACKGROUND:
CREBBP and EP300 mutations occur at a frequency of 15% and 13%, respectively, in small cell lung cancer (SCLC), and preclinical models demonstrated susceptibility to targeting with HDAC inhibitors.METHODS:
Patients with treatment-naïve extensive-stage SCLC, ECOG ≤2 were enrolled and treated with entinostat orally weekly (4 dose levels, DL) in combination with standard dose carboplatin, etoposide, and atezolizumab. Cohort allocation was determined by Bayesian optimal interval (BOIN) design targeting an MTD with a DLT rate of 20%.RESULTS:
Three patients were enrolled and treated at DL1 with entinostat 2 mg. Patients were aged 69-83; 2 male, 1 female; 2 were ECOG 1, and 1 was ECOG 0. The most common adverse events (AEs) were anemia (3), neutropenia (3), thrombocytopenia (2), leukopenia (2), and hypocalcemia (2). Two experienced DLTs during cycle 1 (1) grade (Gr) 4 febrile neutropenia, and (1) Gr 5 sepsis. BOIN design required stopping accrual to DL1, and the trial was closed to further accrual. Entinostat and atezolizumab pharmacokinetics were both comparable to historical controls.CONCLUSION:
Addition of entinostat to atezolizumab, carboplatin, and etoposide is unsafe and resulted in early onset and severe neutropenia, thrombocytopenia. Further exploration of entinostat with carboplatin, etoposide, and atezolizumab should not be explored. (ClinicalTrials.gov Identifier NCT04631029).Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Trombocitopenia
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Carcinoma de Pequenas Células do Pulmão
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Anemia
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Neoplasias Pulmonares
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Neutropenia
Tipo de estudo:
Prognostic_studies
Limite:
Female
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Humans
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Male
Idioma:
En
Revista:
Oncologist
Assunto da revista:
NEOPLASIAS
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
Estados Unidos