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Updated: Jun 11, 2026
Analyzing Tumor and Tissue Distribution of Target Antigen Specific Therapeutic Antibody
Published on: May 16, 2020
A First-in-Class mAb (BI-1607) Targeting FcγRIIB: Preclinical Data and First-in-Human Studies in Patients with
Javier Cortes1,2,3, Araceli Priego1, Elena Garralda4,5,6,7
1Faculty of Biomedical and Health Sciences, Department of Medicine, Universidad Europea de Madrid, Madrid, Spain.
Purpose:
BI-1607 is a human mAb that specifically blocks FcγRIIB, the sole inhibitory Fc receptor and master regulator of humoral and innate immune homeostasis. These studies evaluated preclinical antitumor activity using a BI-1607 murine surrogate (mBI-1607) and the safety, tolerability, pharmacokinetics, and pharmacodynamics of the compound in combination with trastuzumab in patients with HER2-positive advanced solid tumors (NCT05555251).
Patients And Methods:
Immunocompetent syngeneic mouse breast tumor (TUBO) and melanoma (B16-F10) models were used to evaluate in vivo antitumor activity in combination (anti-HER2 and anti-gp75). Ascending doses of BI-1607 administered intravenously every 3 weeks in combination with trastuzumab were evaluated in 18 patients with HER2-positive cancer. The primary objective was to assess the safety and tolerability of BI-1607 by determining dose-limiting toxicities and the maximum tolerated dose or maximum administered dose and identifying a recommended phase 2 dose.
Results:
mBI-1607 enhanced tumor-targeting antibody efficacy and animal survival. BI-1607/trastuzumab was well tolerated, with dose-limiting toxicity (rash) in one patient (5.6%) at 900 mg; the maximum tolerated dose was not reached. Treatment-emergent adverse events grade ≥3 occurred in five patients (28%), including exanthema, increase in liver enzymes, urticaria, acute kidney injury, and aggravated condition. Overall best response was stable disease, observed in seven of the nine evaluable patients (78%). BI-1607 exhibits linear pharmacokinetics for doses above 500 mg, and full receptor saturation was observed throughout the 21 days at 700 mg. No antidrug antibodies were observed.
Conclusions:
The enhancing effect on tumor direct-targeting antibodies observed preclinically, together with the favorable safety profile in patients, supports further investigation of BI-1607.
