First-in-human, phase I study of AK109, an anti-VEGFR2 antibody in patients with advanced or metastatic solid tumors.
ESMO Open
; 8(2): 101156, 2023 04.
Article
em En
| MEDLINE
| ID: mdl-36989884
ABSTRACT
BACKGROUND:
Vascular endothelial growth factor receptor 2 (VEGFR2) plays a key role in antiangiogenesis which has been an essential strategy for cancer treatment. We report the first-in-human study of AK109, a novel anti-VEGFR2 monoclonal antibody, to characterize the safety profile and pharmacokinetics/pharmacodynamics (PK/PD) properties, and explore the preliminary antitumor efficacy in patients with solid tumors. PATIENTS ANDMETHODS:
This was a multicenter, open-label, phase I study, including dose escalation and dose expansion (NCT04547205). Patients with advanced cancers were treated 2 and 3 weekly with escalating doses of AK109. A 3 + 3 design was used to determine the maximum tolerated dose. Blood was sampled for PK/PD analysis. The primary endpoint was safety and recommended phase II dose (RP2D).RESULTS:
A total of 40 patients were enrolled. No dose-limiting toxicity was observed. However, 38 patients reported treatment-related adverse events (TRAEs); grade ≥3 TRAEs occurred in 10 patients. The most common TRAEs were proteinuria (n = 24, 60%), hypertension (n = 13, 32.5%), increased aspartate transaminase (n = 11, 27.5%), thrombopenia (n = 10, 25%), and anemia (n = 10, 25%). A total of 28 patients (70%) reported adverse events of special interest (AESIs). The most common AESIs were proteinuria (60%), hypertension (32.5%), and hemorrhage (32.5%), mainly including gum bleeding and urethrorrhagia. AK109 exhibited an approximately linear PK exposure with dose escalation at 2-12 mg/kg. PD analyses showed rapid target engagement. Among the 40 patients, 4 achieved partial response and 21 achieved stable disease with an objective response rate of 10% and a disease control rate of 62.5%. Based on the safety profile, the PK/PD profile, and preliminary antitumor activities, 12 mg/kg Q2W and 15 mg/kg Q3W were selected as RP2D.CONCLUSIONS:
AK109 showed manageable safety profile and promising antitumor activity, supporting further clinical development in a large population.Palavras-chave
Texto completo:
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Receptor 2 de Fatores de Crescimento do Endotélio Vascular
/
Neoplasias
Tipo de estudo:
Clinical_trials
Limite:
Humans
Idioma:
En
Revista:
ESMO Open
Ano de publicação:
2023
Tipo de documento:
Article