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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 36
Issue 15
Date 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
Unknown unknown nasopharynx carcinoma not applicable BI 836880 Case Reports/Case Series Actionable In a Phase I trial, BI 836880 treatment was well tolerated in patients with advanced solid tumors, and resulted in 2 partial responses (n=29), including a partial response in a patient with nasopharyngeal carcinoma (J Clin Onc 2018 36:15_suppl, 12024; NCT02674152). detail...
Unknown unknown Advanced Solid Tumor not applicable BI 836880 Phase I Actionable In a Phase I trial, BI 836880 treatment was well tolerated, and resulted in partial response in 7% (2/29) and stable disease in 31% (9/29) of patients with advanced solid tumors (J Clin Onc 2018 36:15_suppl, 12024; NCT02674152). detail...
Unknown unknown breast carcinoma not applicable BI 836880 Case Reports/Case Series Actionable In a Phase I trial, BI 836880 treatment was well tolerated in patients with advanced solid tumors, and resulted in 2 partial responses (n=29), including a partial response in a patient with breast carcinoma (J Clin Onc 2018 36:15_suppl, 12024; NCT02674152). detail...