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
Le Tourneau, C. (Paris-Saclay University)
Becker, H. (University of Freiburg)
Claus, R. (Medical Faculty Augsburg University)
Elez, Elena (Vall d'Hebron Institut d'Oncologia)
Ricci, F. (Paris-Saclay University)
Fritsch, R. (University of Freiburg)
Silber, Y. (Medical Faculty Augsburg University)
Hennequin, A. (Centre Georges-François Leclerc)
Tabernero, Josep (Vall d'Hebron Institut d'Oncologia)
Jayadeva, G. (Boehringer Ingelheim International GmbH)
Luedtke, D. (Boehringer Ingelheim Pharma GmbH and Co KG)
He, M. (Boehringer Ingelheim Pharmaceuticals Inc.)
Isambert, N. (Centre Georges-François Leclerc)
Universitat Autònoma de Barcelona

Data:	2022
Resum:	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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Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Advanced solid tumors ; Angiopoietin-2 ; Nanobody ; Phase I ; Vascular endothelial growth factor
Publicat a:	ESMO open, Vol. 7 (september 2022) , ISSN 2059-7029

DOI: 10.1016/j.esmoop.2022.100576
PMID: 36108560

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