Abstract Background: TAVO412 has two anti-EGFR nanobody-like domains, an anti-cMET Fab arm, and an anti-VEGF single-chain variable fragment, with enhanced Fc effector functions. It is designed to use avidity to inhibit EGFR ligand binding and receptor heterodimerization, shut down cMET signaling, and sequester soluble VEGF-A in the EGFR/cMET-high tumor microenvironments. TAVO412 has demonstrated robust antitumor activities in multiple solid tumor cell line-derived and NSCLC patient sample-derived xenograft models, supporting its clinical evaluation. Methods: TAVO412-CN001 (NCT06761651) is a two-part, open-label Phase I study evaluating the safety, tolerability, and preliminary antitumor activity of TAVO412 in patients with advanced or metastatic solid tumors refractory to standard therapies. Here we report the preliminary results from Part A that uses a standard 3+3 design for dose-escalation up to 1500 mg, with backfill in relevant cohorts to further assess safety and preliminary efficacy1, 2. 3. Results: As of Dec. 30, 2025, 67 patients, with 6 tumor types (NSCLC n=33, ESCC n=13, CRC n=18, and n=1 each in liver, gastric and breast cancer), were enrolled in 5 dose cohorts from 150 to 1500 mg, q2w, in Part A. Nine patients still remain on the treatment. Serum drug exposures increased with the dose in a target mediated drug-disposition manner. TAVO412 had low immunogenicity (6%). No DLTs were reported and the MTD had not been reached. The most common treatment-emergent (TE) AEs (≥30%) across all doses were rash, hypoalbuminemia, stomatitis, infusion related reaction, increase ALT, and hypokalemia. Preliminary efficacy signals were observed in efficacy-evaluable NSCLC patients (n=27) with 5 PRs (3 of 9 EGFR Exon20ins and 2 of 12 Exon21 L858R) and 13 SDs, in ESCC (n=11) with 1 PR and 8 SDs, and in CRC (n=15) with 4 PRs and 9 SDs, in the dose range from 375 to 1500 mg. Most PRs were confirmed. The longest treatment duration was approximately 38 weeks. The baseline serum soluble free VEGF A levels correlated with the responses. Conclusion: TAVO412 was well tolerated up to 1500 mg with a manageable safety profile. Preliminary activities of TAVO412 have been observed in CRC, ESCC, and NSCLC patients who had been heavily pretreated. Further evaluation of TAVO412 in patients with these type of tumors is warranted. Ethics Approval: This study was approved by the CRADL-Suzhou Ethics Board (P202302160002), NMPA IND (2023LP01660), and Henan Cancer Hospital Ethics Board (2023-314-003). References. 1Front Oncol. (2025) 15: 1533059. doi: 10. 3389/fonc. 2025. 1533059. eCollection 2025. 2 Cancer Res (2025) 85 (8Supp₂): CT185. doi. org/10. 1158/1538-7445. AM2025-CT1853Front. Immunol. Sec. Cancer Immunity and Immunotherapy (2025) Vol 16 doi. org/10. 3389/fimmu. 2025. 1505868 Citation Format: Mark Chiu, Yanjiao Yu, Mira Zhao, Wei Zhang, Hong Xie, Chao Han. Preliminary clinical results of TAVO412, an anti-EGFR/cMET/VEGF multispecific antibody, in patients with advanced or metastatic solid tumors abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts) ; 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86 (8Suppl): Abstract nr CT050.
Chiu et al. (Fri,) studied this question.