Preclinical and phase I studies of KA2237, a selective and potent inhibitor of PI3K ß/δ in relapsed refractory B cell lymphoma.
Leuk Lymphoma
; 62(14): 3452-3462, 2021 12.
Article
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| MEDLINE
| ID: mdl-34365878
ABSTRACT
PI3-kinase p110δ is mainly expressed in lymphocytes and is an attractive therapeutic target in B cell lymphomas. Targeting p110ß may further suppress tumor growth and overcome escape mechanisms. KA2237 is an oral, potent, dual p110ß/p110δ inhibitor. In preclinical studies, KA2237 inhibited p110ß- and p110δ-dependent AKT activation and suppressed proliferation of diverse hematological and epithelial tumors. Twenty-one patients received KA2237 in a first-in-human phase I study (NCT02679196; diffuse large B cell, n = 8; follicular, n = 5; mantle cell, n = 3; chronic lymphocytic leukemia/small lymphocytic lymphoma, n = 3; marginal zone, n = 1; Waldenstrom's, n = 1). Median age 69; median prior therapies 3. Eighty-six percent of patients experienced treatment-related adverse events (TRAEs). Forty-three percent of patients experienced grade ≥3 TRAEs, with rash (n = 3), pneumonia (n = 3), transaminitis (n = 2), and pneumonitis (n = 2) being most common. Thirty-three percent discontinued treatment due to adverse events. KA2237 induced objective responses in indolent and aggressive lymphoma (overall response rate 37%; complete response n = 4, partial response n = 3).
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Linfoma no Hodgkin
/
Linfoma de Células B
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Linfoma Folicular
Límite:
Aged
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Humans
Idioma:
En
Revista:
Leuk Lymphoma
Asunto de la revista:
HEMATOLOGIA
/
NEOPLASIAS
Año:
2021
Tipo del documento:
Article
País de afiliación:
Estados Unidos
Pais de publicación:
EEUU
/
ESTADOS UNIDOS
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ESTADOS UNIDOS DA AMERICA
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EUA
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UNITED STATES
/
UNITED STATES OF AMERICA
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US
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USA