A First-in-Class mAb (BI-1607) Targeting FcγRIIB: Preclinical Data and First-in-Human Studies in Patients with HER2-Positive Advanced Solid Tumors

  • Clin Cancer Res. 2025 Dec 1;31(23):4953-4963. doi: 10.1158/1078-0432.CCR-25-1348.
Javier Cortés  1  2  3 ,  Araceli Priego  1 ,  Elena Garralda  4  5  6  7 ,  Katerin Rojas  4 ,  Simon R Lord  8 ,  Thorsten O Goetze  9 ,  Sherko Kuemmel  10  11 ,  Simon J Crabb  12 ,  Zinnia P Parra-Guillen  13 ,  Marie Borggren  13 ,  Ingrid Karlsson  13 ,  Danijela Lindahl  13 ,  Linda Mårtensson  13 ,  Robert Oldham  14 ,  Anna Ropenga  13 ,  Ingrid Teige  13 ,  Johan Wallin  13 ,  Björn Frendeus  13 ,  Andres McAllister  13
Affiliations
  • 1. Faculty of Biomedical and Health Sciences, Department of Medicine, Universidad Europea de Madrid, Madrid, Spain.
  • 2. International Breast Cancer Center (IBCC), Pangaea Oncology, Quironsalud Group, Barcelona, Spain.
  • 3. IOB Madrid, Institute of Oncology, Hospital Beata Maria Ana, Madrid, Spain.
  • 4. Research Unit for Molecular Therapy of Cancer (UITM), Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain.
  • 5. Early Drug Development Group, Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain.
  • 6. Oncology Department, Hospital Universitario Vall d'Hebron (HUVH), Barcelona, Spain.
  • 7. Phase I Unit - NEXT Oncology, Hospital Quirónsalud, Barcelona, Spain.
  • 8. Department of Oncology, University of Oxford, Oxford, United Kingdom.
  • 9. Institut of Clinical Cancer Research, UCT-University Cancer Center Frankfurt, Frankfurt, Germany.
  • 10. Interdisciplinary Breast Unit, Kliniken Essen-Mitte, Essen, Germany.
  • 11. Department of Gynecology with Breast Center, Charité - Universitätsmedizin Berlin, Berlin, Germany.
  • 12. Southampton Experimental Cancer Medicine Centre, University of Southampton, Southampton, United Kingdom.
  • 13. BioInvent International AB, Lund, Sweden.
  • 14. Antibody and Vaccine Group, Centre for Cancer Immunology, University of Southampton, Southampton, United Kingdom.
PMID: 41071338 DOI: 10.1158/1078-0432.CCR-25-1348
Abstract

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.

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