A first-in-class monoclonal antibody (BI-1607) targeting FcγRIIB: preclinical data and first-in-human studies in patients with HER2-positive advanced solid tumors
A first-in-class monoclonal antibody (BI-1607) targeting FcγRIIB: preclinical data and first-in-human studies in patients with HER2-positive advanced solid tumors
Purpose: BI-1607 is a human monoclonal antibody that specifically blocks FcγRIIB, 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 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 three weeks in combination with trastuzumab were evaluated in 18 HER2-positive cancer patients. The primary objective was to assess safety and tolerability of BI-1607 by determining dose-limiting toxicities, maximum tolerated dose (MTD) 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 1 patient (5.6 %) at 900 mg; the MTD was not reached. Treatment-emergent adverse events grade ≥3 occurred in 5 patients (28 %), including exanthema, increase in liver enzymes, urticaria, acute kidney injury, and aggravated condition. Overall best response was stable disease, observed in 7 out of the 9 evaluable patients (78 %). BI-1607 exhibits linear pharmacokinetics for doses above 500 mg, and full receptor saturation throughout the 21 days at 700 mg. No ADAs were observed.
Conclusions: the enhancing effect on tumor direct-targeting antibodies observed preclinically, together with the favorable safety profile in patients support further investigation of BI-1607.
4953-4963
Cortés, Javier
7a31c139-cf07-4268-9328-54f99427d208
Priego, Araceli
d799de7a-2aba-454f-9b8d-04daf602a95c
Garralda, Elena
1f8a2b00-a670-4f15-827b-23599e723459
Crabb, Simon J.
bcd1b566-7677-4f81-8429-3ab0e85f8373
Oldham, Robert
844b9bff-16f0-4577-abba-b35afd02b923
Cortés, Javier
7a31c139-cf07-4268-9328-54f99427d208
Priego, Araceli
d799de7a-2aba-454f-9b8d-04daf602a95c
Garralda, Elena
1f8a2b00-a670-4f15-827b-23599e723459
Crabb, Simon J.
bcd1b566-7677-4f81-8429-3ab0e85f8373
Oldham, Robert
844b9bff-16f0-4577-abba-b35afd02b923
Cortés, Javier, Priego, Araceli and Garralda, Elena
,
et al.
(2025)
A first-in-class monoclonal antibody (BI-1607) targeting FcγRIIB: preclinical data and first-in-human studies in patients with HER2-positive advanced solid tumors.
Clinical Cancer Research, 31 (23), .
(doi:10.1158/1078-0432.CCR-25-1348).
Abstract
Purpose: BI-1607 is a human monoclonal antibody that specifically blocks FcγRIIB, 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 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 three weeks in combination with trastuzumab were evaluated in 18 HER2-positive cancer patients. The primary objective was to assess safety and tolerability of BI-1607 by determining dose-limiting toxicities, maximum tolerated dose (MTD) 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 1 patient (5.6 %) at 900 mg; the MTD was not reached. Treatment-emergent adverse events grade ≥3 occurred in 5 patients (28 %), including exanthema, increase in liver enzymes, urticaria, acute kidney injury, and aggravated condition. Overall best response was stable disease, observed in 7 out of the 9 evaluable patients (78 %). BI-1607 exhibits linear pharmacokinetics for doses above 500 mg, and full receptor saturation throughout the 21 days at 700 mg. No ADAs were observed.
Conclusions: the enhancing effect on tumor direct-targeting antibodies observed preclinically, together with the favorable safety profile in patients support further investigation of BI-1607.
Text
ccr-25-1348 (1)
- Accepted Manuscript
Text
BI1607 pre-clinical main + suppl
- Version of Record
More information
Accepted/In Press date: 7 October 2025
e-pub ahead of print date: 10 October 2025
Additional Information:
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.
Identifiers
Local EPrints ID: 508366
URI: http://eprints.soton.ac.uk/id/eprint/508366
ISSN: 1078-0432
PURE UUID: 1f31415d-0983-4463-b36c-abff1678ffca
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Date deposited: 20 Jan 2026 17:41
Last modified: 24 Jan 2026 02:59
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Author:
Javier Cortés
Author:
Araceli Priego
Author:
Elena Garralda
Author:
Robert Oldham
Corporate Author: et al.
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