Two phase I studies of BI 836880, a vascular endothelial growth factor/angiopoietin-2 inhibitor, administered once every 3 weeks or once weekly in patients with advanced solid tumors

BI 836880 is a humanized bispecific nanobody® that inhibits vascular endothelial growth factor and angiopoietin-2. Here, we report results from two phase I, nonrandomized, dose-escalation studies (NCT02674152 and NCT02689505; funded by Boehringer Ingelheim) evaluating BI 836880 in patients with conf...

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Detalles Bibliográficos
Autores: Le Tourneau, Christophe|||0000-0001-9772-4686, Becker, Holger, Claus, Rainer|||0000-0003-2617-8766, Elez, Elena|||0000-0002-4653-6324, Ricci, Francesco, Fritsch, Ralph|||0000-0001-9639-3213, Silber, Y., Hennequin, Audrey|||0000-0001-8043-1836, Tabernero, Josep|||0000-0002-2495-8139, Jayadeva, Girish, Luedtke, Doreen, He, Min, Isambert, Nicolas
Tipo de recurso: artículo
Fecha de publicación:2022
País:España
Institución:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:283621
Acceso en línea:https://ddd.uab.cat/record/283621
https://dx.doi.org/urn:doi:10.1016/j.esmoop.2022.100576
Access Level:acceso abierto
Palabra clave:Advanced solid tumors
Angiopoietin-2
Nanobody
Phase I
Vascular endothelial growth factor
Descripción
Sumario:BI 836880 is a humanized bispecific nanobody® that inhibits vascular endothelial growth factor and angiopoietin-2. Here, we report results from two phase I, nonrandomized, dose-escalation studies (NCT02674152 and NCT02689505; funded by Boehringer Ingelheim) evaluating BI 836880 in patients with confirmed locally advanced or metastatic solid tumors, refractory to standard therapy, or for which standard therapy was ineffective. Patients aged ≥18 years, with an Eastern Cooperative Oncology Group performance status of 0-2 and adequate organ function received escalating intravenous doses of BI 836880 once every 3 weeks (Q3W; Study 1336.1) or once weekly (QW; Study 1336.6). Primary objectives were maximum tolerated dose (MTD) and recommended phase II dose of BI 836880, based on dose-limiting toxicities (DLTs) during the first cycle. Patients received one of five dosages of 40-1000 mg Q3W (29 patients) or 40-240 mg QW (24 patients). One DLT occurred with Q3W treatment [Grade (G) 3 pulmonary embolism (1000 mg)]. Five DLTs occurred in four patients treated QW [G2 proteinuria (120 mg); G3 hypertension (180 mg); G3 proteinuria and G3 hypertension (240 mg); and G4 respiratory distress (240 mg)]. All patients experienced adverse events, most commonly hypertension with Q3W treatment (89.7%; G3 41.4%), and asthenia with QW treatment (62.5%). Two patients treated Q3W (both 1000 mg) and three patients treated QW (120 mg, 2 patients; 180 mg, 1 patient) experienced partial response. The MTD of BI 836880 was 720 mg Q3W and 180 mg QW. BI 836880 was generally manageable and demonstrated preliminary efficacy. ; and NCT02689505;

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