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Updated: Jun 11, 2026
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Analyzing Tumor and Tissue Distribution of Target Antigen Specific Therapeutic Antibody
Published on: May 16, 2020
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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.
Summary
BI-1607, a novel antibody, enhances antitumor activity when combined with trastuzumab in HER2-positive cancers. The combination demonstrated a favorable safety profile, supporting further clinical investigation for advanced solid tumors.
Area of Science:
- Immunology and Oncology
- Pharmacology and Therapeutics
Background:
- BI-1607 is a human monoclonal antibody (mAb) that targets FcγRIIB, a key regulator of immune homeostasis.
- FcγRIIB blockade is a potential strategy to enhance immune responses against tumors.
Purpose of the Study:
- To evaluate the preclinical antitumor activity of a BI-1607 murine surrogate (mBI-1607).
- To assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of BI-1607 in combination with trastuzumab in patients with HER2-positive advanced solid tumors.
Main Methods:
- Preclinical studies utilized immunocompetent syngeneic mouse models (TUBO and B16-F10) to assess in vivo antitumor activity.
- A Phase 1 study involved escalating doses of BI-1607 intravenously every 3 weeks in combination with trastuzumab in 18 patients with HER2-positive cancer.
- Primary objectives included safety assessment, dose-limiting toxicities, maximum tolerated dose (MTD), and recommended Phase 2 dose (RP2D) determination.
Main Results:
- mBI-1607 demonstrated enhanced tumor-targeting antibody efficacy and improved animal survival in preclinical models.
- The BI-1607/trastuzumab combination was generally well tolerated, with rash as the dose-limiting toxicity in one patient at 900 mg; MTD was not reached.
- Grade ≥3 treatment-emergent adverse events occurred in 28% of patients. Stable disease was the best overall response in 78% of evaluable patients. BI-1607 exhibited linear pharmacokinetics and achieved full FcγRIIB saturation.
Conclusions:
- The preclinical enhancement of tumor-targeting antibodies by BI-1607, coupled with its favorable safety profile in patients, warrants further investigation.
- BI-1607 shows promise as a combination therapy to improve outcomes in HER2-positive advanced solid tumors.
