ORIGINAL RESEARCH article
Front. Oncol.
Sec. Cancer Molecular Targets and Therapeutics
Volume 15 - 2025 | doi: 10.3389/fonc.2025.1533059
This article is part of the Research TopicInnovative Drug Combinations for Enhanced Solid Tumor Treatment EfficacyView all 3 articles
A Trispecific Antibody targeting EGFR/cMET/VEGF Demonstrates Multiple Mechanisms of Action to inhibit Wild-Type and Mutant NSCLC Animal Models
Provisionally accepted
Mark L Chiu*
Karen Jin
Ping SunPeng ChenYuqiang XuGuangmao MuZhengxia ZhaSimin WuMeixia FuHao JiangSheng HuangFulai Zhou
Chao Han- Tavotek Biotherapeutics, Lower Gwynedd, United States
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Non-small cell lung cancer (NSCLC) patients who do not respond to standard of care treatment can have activating mutations in the epidermal growth factor receptor (EGFR) and mesenchymal epithelial transition factor (cMET) signaling pathways, as well as having enhanced levels of vascular endothelial growth factor (VEGF). To combat such resistance mechanisms, TAVO412, was engineered to control aberrant cMET, VEGF-A, and EGFR activities. TAVO412 robustly suppressed ligand-induced phosphorylation of EGFR and cMET in NSCLC cell lines. TAVO412 demonstrated more potent antitumor activity than amivantamab and cetuximab in NSCLC xenograft models using cell lines with varying levels of mutant and wild-type EGFR and cMET. In addition, TAVO412 had both EGFR/cMET receptor degradation and enhanced Fc effector functions for tumor cell cytotoxicity. Moreover, TAVO412 in combination with osimertinib, lazertinib, docetaxel, and radiotherapy, resulted in complete and durable regression of NSCLC xenograft tumors.
Keywords: trispecific antibodies, NSCLC, EGFR cancer cells +, cmet, VEGF
Received: 23 Nov 2024; Accepted: 23 Apr 2025.
Copyright: © 2025 Chiu, Jin, Sun, Chen, Xu, Mu, Zha, Wu, Fu, Jiang, Huang, Zhou and Han. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Mark L Chiu, Tavotek Biotherapeutics, Lower Gwynedd, United States
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