Phase 1 study of the anti-vascular endothelial growth factor receptor 3 monoclonal antibody LY3022856/IMC-3C5 in patients with advanced and refractory solid tumors and advanced colorectal cancer.
Cancer Chemother Pharmacol
; 78(4): 815-24, 2016 Oct.
Article
em En
| MEDLINE
| ID: mdl-27566701
ABSTRACT
PURPOSE:
Metastasis of solid tumors to regional lymph nodes is facilitated by tumor lymphangiogenesis, which is primarily mediated by the vascular endothelial growth factor receptor 3 (VEGFR-3). We conducted a phase 1 dose-escalation (part A) study of the VEGFR-3 human immunoglobulin G subclass 1 monoclonal antibody LY3022856 in advanced solid tumors, followed by a colorectal cancer (CRC) expansion (part B).METHODS:
Part A evaluated the safety profile and maximum tolerated dose (MTD) of LY3022856 in patients treated intravenously at doses of 5-30 mg/kg weekly (qwk). Part B further evaluated tolerability in CRC patients treated with 30 mg/kg. Secondary objectives were pharmacokinetics, anti-tumor activity, and pharmacodynamics (exploratory).RESULTS:
A total of 44 patients (23 in part A; 21 in part B) were treated; only one dose-limiting toxicity was observed at the lowest dose level. The MTD was not reached. Treatment-emergent adverse events (TEAEs) of any grade included in ≥15 % of all patients were nausea (41 %), fatigue (32 %), vomiting (30 %), decreased appetite (27 %), pyrexia (25 %), peripheral edema (23 %), and urinary tract infection (UTI, 20 %). The most common grade 3/4 TEAEs included UTI and small intestinal obstruction (7 % each). No radiographic responses were noted. Median progression-free survival in part B was 6.3 weeks (95 % confidence interval 5.1, 14.4), and a best overall response of stable disease was observed in 4 CRC patients (19.0 %).CONCLUSIONS:
LY3022856 was well tolerated up to a dose of 30 mg/kg qwk, but with minimal anti-tumor activity in CRC. CLINICALTRIALS. GOV IDENTIFIER NCT01288989.Palavras-chave
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Neoplasias Colorretais
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Receptor 3 de Fatores de Crescimento do Endotélio Vascular
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Anticorpos Monoclonais
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Neoplasias
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Antineoplásicos
Tipo de estudo:
Clinical_trials
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Etiology_studies
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Incidence_studies
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Observational_studies
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Prognostic_studies
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Risk_factors_studies
Limite:
Adult
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Aged
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Cancer Chemother Pharmacol
Ano de publicação:
2016
Tipo de documento:
Article
País de afiliação:
Estados Unidos