Preclinical studies of BB-1701, a HER2-targeting eribulin-containing ADC with potent bystander effect and ICD activity.

BACKGROUND

Several HER2-targeting antibody-drug conjugates (ADC) have gained market approval for the treatment of HER2-expressing metastasis. Promising responses have been reported with the new generation of ADCs in patients who do not respond well to other HER2-targeting therapeutics. However, these ADCs still face challenges of resistance and/or severe adverse effects associated with their particular payload toxins. Eribulin, a therapeutic agent for the treatment of metastatic breast cancer and liposarcoma, is a new choice of ADC payload with a distinct mechanism of action and safety profile.

METHODS

We've generated a novel HER2-tageting eribulin-containing ADC, BB-1701. The potency of BB-1701 was tested

RESULTS

In comparison with HER2-targeting ADCs with DM1 and Dxd payload, eribulin-containing ADC demonstrated higher

CONCLUSIONS

The preclinical data support the test of BB-1701 in patients with various HER2-expressing cancers, including those resistant to other HER2-targeting ADCs. A phase I clinical trial of BB-1701 (NCT04257110) in patients is currently underway.

Informations de copyright

Published by Oxford University Press on behalf of Antibody Therapeutics 2024.

Déclaration de conflit d'intérêts

The authors declare the following financial interests/personal relationships that may be considered as potential competing interests: This study was supported by Bliss Biopharmaceutical (Hangzhou), Co., Ltd. Yang Wang, Bing Xia, Lixia Cao, Jianfeng Yang, Cui Feng, Fangdun Jiang, Chen Li, Lixia Gu, Yifan Yang, Jing Tian, Ziping Wei, and Yuhong Zhou are current employees and shareholders of Bliss Biopharmaceutical. Xin Cheng, Keiji Furuuchi, James Fulmer, Arielle Verdi, Katherine Rybinski, Allis Soto, Earl Albone, and Toshimitsu Uenaka are current employees of Eisai Inc. There are no other conflicts of interest to declare.