2026-04-13T04:01:35Zhttps://recercat.cat/oai/requestoai:recercat.cat:11351/143822026-03-24T07:26:27Zcom_2072_378070com_2072_378040col_2072_378092
RECERCAT
author
PRIEGO, ARACELI
author
Rojas Laimito, Katerin
author
lord, simon
author
Goetze, Thorsten
author
Cortes, Javier
author
GARRALDA, Elena
2026-03-24T07:26:27Z
2026-03-24T07:26:27Z
2026-03-23T10:59:18Z2026-03-23T10:59:18Z2025-12-01
https://hdl.handle.net/11351/14382
Monoclonal antibody; Solid tumors; HER2 positiveAnticuerpo monoclonal; Tumores sólidos; HER2 positivoAnticòs monoclonal; Tumors sòlids; HER2 positiuPurpose:
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.This study was sponsored by Bioinvent International AB. The murine FcγRII-specific antibody clone AT-130-2 was a kind gift from Professor Mark Cragg (University of Southampton). We wish to thank all the patients, family members, and staff from all the units that participated in the study.
Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/ info:eu-repo/semantics/openAccess
Mama - Càncer - Tractament
Posologia
Anticossos monoclonals - Ús terapèutic
Medicaments - Relacions dosi-efecte
Rates (Animals de laboratori)
DISEASES::Neoplasms::Neoplasms by Site::Breast Neoplasms
CHEMICALS AND DRUGS::Amino Acids, Peptides, and Proteins::Proteins::Blood Proteins::Immunoproteins::Immunoglobulins::Antibodies::Antibodies, Monoclonal
Other subheadings::Other subheadings::Other subheadings::/administration & dosage
ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Investigative Techniques::Toxicity Tests::Maximum Tolerated Dose
ORGANISMS::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Eutheria::Rodentia::Muridae::Murinae::Mice
ENFERMEDADES::neoplasias::neoplasias por localización::neoplasias de la mama
COMPUESTOS QUÍMICOS Y DROGAS::aminoácidos, péptidos y proteínas::proteínas::proteínas sanguíneas::inmunoproteínas::inmunoglobulinas::anticuerpos::anticuerpos monoclonales
Otros calificadores::Otros calificadores::Otros calificadores::/administración & dosificación
TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::técnicas de investigación::pruebas de toxicidad::dosis máxima tolerada
ORGANISMOS::Eukaryota::animales::Chordata::vertebrados::mamíferos::Eutheria::Rodentia::Muridae::Murinae::ratones
A First-in-Class mAb (BI-1607) Targeting FcγRIIB: Preclinical Data and First-in-Human Studies in Patients with HER2-Positive Advanced Solid Tumors
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion