Abstract CT185: Trispecific EGFR x cMET x VEGF antibody, TAVO412, has clinical responses in esophageal and lung cancers

Background: Abnormal EGFR signaling, increased cMET activation, and VEGF-induced angiogenesis are responsible for the growth and metastasis of many difficult to treat solid tumors. TAVO412 is a humanized multi-specific antibody with two distinct anti-EGFR nanobody-like domains, an anti-cMET Fab arm, and an anti-VEGF ScFv domain. In addition, the Fc domain allows for the heterodimerization, antibody-like pharmacokinetic profile, and additional mutations that enhance the Fc effector functions. TAVO412 had strong in vivo tumor growth inhibition in the preclinical models of NSCLC, gastrointestinal and esophageal cancers, PDAC, TNBC, and other solid tumor models. TAVO412 also had strong tumor growth inhibition as demonstrated against NSCLC patient derived xenograft (PDX) models with various mutant EGFR and cMet genotypes. Stronger activities were also demonstrated when TAVO412 was in combination with docetaxel, TKIs, and with radiotherapy. Methods: The clinical study (TAVOTEK412-CN001) is a two-part, open-label, non-randomized, Phase I study to determine the safety and tolerability, to define the MTD/RP2D, and to assess the preliminary efficacy of TAVO412 in patients with advanced or metastatic solid tumors who progressed on prior standard-of-care therapies (Clinical trial NCT06761651). Part 1 of the study is a dose escalation by a standard 3+3 design, mainly for safety and tolerability with 5 dose cohorts up to 1500 mg. Part 2 of the study is an extension of the study in about 100 patients based on the preliminary information obtained in Part 1 regarding dose levels, type of tumor showing preliminary efficacy signals, and genetic makeup. At the time of this abstract, 25 patients with a variety of solid tumors have been enrolled in Part 1 dose escalation. Since no DLT have been observed and MTD has not been reached, an additional dose level at 1750 mg will be tested. Meanwhile, the safety and efficacy signals are being enhanced by the backfill of patients to the safe and potential efficacious dose cohorts starting Q1 2025. The Part 2 of the study is expected to start in Q4 2025. Keywords: trispecific antibody, EGFR, cMET, VEGF, gastrointestinal cancers, lung cancersEthics approval: “This study was approved by CRADL-Suzhou’s Ethics Board; approval number P202302160002.NMPA IND Approval number 2023LP01660; Henan Cancer Hospital Ethics Board approval number 2023-314-003 Citation Format: Mark Chiu, Wei Zhang, Yanjiao Yu, Helen Jiang, Chao Han. Trispecific EGFR x cMET x VEGF antibody, TAVO412, has clinical responses in esophageal and lung cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 2 (Late-Breaking, Clinical Trial, and Invited s); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_2): nr CT185.