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.
Cortés et al. (2025) studied this question.