Phase 1a study of the CDK4/6 inhibitor, FCN-437c, in Chinese patients with HR + /HER2- advanced breast cancer.
Invest New Drugs
; 39(6): 1549-1558, 2021 12.
Article
en En
| MEDLINE
| ID: mdl-34109484
ABSTRACT
Purpose This phase 1a, first-in-human study assessed the safety, maximum tolerated dose (MTD), pharmacokinetics (PK), and antitumor activity of FCN-437c, a cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor. Methods The study enrolled female patients with HR + /HER2- advanced breast cancer (BC) who failed standard of care therapy. A 3 + 3 dose-escalation design was utilized with a starting dose of 50 mg daily for 3 weeks on and 1 week off treatment in 28-day cycles. Patients received escalating doses of FCN-437c monotherapy (50, 100, 200, 300, and 450 mg). Results Seventeen patients received FCN-437c 50 mg (n = 3), 100 mg (n = 3), 200 mg (n = 3), 300 mg (n = 6), and 450 mg (n = 2). Two patients who received the 450-mg dose experienced dose-limiting toxicities (DLTs; grade 4 thrombocytopenia and neutropenia); no DLT was observed at any other dose level. Frequently reported treatment-emergent adverse events (TEAEs) of any grade were hematological leukopenia (94.1%), neutropenia (88.2%), anemia (64.7%), and thrombocytopenia (47.1%). Grade 3-4 TEAEs included neutropenia (64.7%) and leukopenia (47.1%). Exposure of FCN-437c increased almost proportionally to doses ranging from 50 to 200 mg. At doses from 200 to 450 mg, there appeared to be a trend of saturation. The MTD was determined to be 300 mg. Of 15 patients with measurable disease, nine (60.0%) patients experienced stable disease; no complete or partial responses were observed. Conclusions These results established an acceptable safety profile for FCN-437c in patients with advanced BC, and there were no unexpected signals relative to other CDK4/6 inhibitors. (NCT04488107; July 13, 2020).
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Neoplasias de la Mama
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Inhibidores de Proteínas Quinasas
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Quinasa 4 Dependiente de la Ciclina
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Antineoplásicos
Tipo de estudio:
Clinical_trials
/
Prognostic_studies
Límite:
Adult
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Aged
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Female
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Humans
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Middle aged
País/Región como asunto:
Asia
Idioma:
En
Revista:
Invest New Drugs
Año:
2021
Tipo del documento:
Article
País de afiliación:
China