Reference Detail

Ref Type

PMID

Authors

Christophe Le Tourneau, Rainer Claus, Francesco Ricci, Bjorn Hackanson, Christoph Rummelt, Oliver Fietz, Thomas Arnhold, Dooti Roy, Zohra Oum'Hamed, Ralph M Fritsch

Title

First-in-human phase I trial of BI 836880, a vascular endothelial growth factor (VEGF)/angiopoietin-2 (Ang-2)-blocking nanobody, given every 3 weeks (q3w) in patients (pts) with advanced/metastatic solid tumors.

Journal	Vol	Issue	Date	Pages	Journal Short Title
	36	15	2018

URL

https://ascopubs.org/doi/abs/10.1200/JCO.2018.36.15_suppl.12024

Abstract Text

Background: VEGF and Ang-2 inhibitors have demonstrated clinical activity in various tumor types. Given the overlap of the VEGF/VEGFR2 and Ang-2/Tie-2 signaling pathways there is a rationale for dual inhibition. BI 836880 is a humanized bispecific nanobody (engineered antibody fragment of variable antibody domains) that inhibits VEGF and Ang2 and has demonstrated preclinical activity in cancer models. Methods: Pts with solid tumors refractory after standard therapies/for whom no established treatment options were available received BI 836880 q3w (IV; starting dose 40 mg). Dose escalation followed a Bayesian logistic regression model with overdose control. The maximum-tolerated dose (MTD; primary endpoint) was evaluated based on dose-limiting toxicities (DLTs) in the first 21-day cycle. Treatment-related AEs (TRAEs) leading to dose reduction/discontinuation, exposure/disposition kinetic measures (both secondary endpoints) and best overall response were also assessed. Results: 29 pts were treated: median age 57 yrs (range 28–79); 62% female. The MTD was determined as BI 836880 720 mg q3w (Table). All pts had at least 1 AE, most commonly (all grade/grade ≥3): hypertension 86%/34%, asthenia 48%/10%, nausea 45%/3% and vomiting 38%/3%. 23 (79%) pts had TRAEs; none led to dose reduction. One patient had a TRAE leading to discontinuation (pulmonary embolism DLT at 1000 mg). Two (7%) pts (nasopharyngeal [n = 1] and breast [n = 1] carcinoma) had a partial response and 9 (31%) pts had stable disease. PK/PD analysis of 14 evaluable pts showed dose-proportional plasma kinetics of BI 836880, complete peripheral target inhibition at doses ≥360 mg q3w and predicted required trough values at doses ≥720 mg q3w. Clinical trial information: NCT02674152. Conclusions: The MTD/recommended phase 2 dose of BI 836880 was determined as 720 mg q3w based on safety and PK/PD analyses. Early signs of antitumor activity were observed.

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Molecular Profile	Treatment Approach

Gene Name	Source	Synonyms	Protein Domains	Gene Description	Gene Role

Therapy Name	Drugs	Efficacy Evidence	Clinical Trials

Drug Name	Trade Name	Synonyms	Drug Classes	Drug Description

Gene	Variant	Impact	Protein Effect	Variant Description	Associated with drug Resistance

Molecular Profile	Indication/Tumor Type	Response Type	Therapy Name	Approval Status	Evidence Type	Efficacy Evidence	References