Abstract FGFR2b overexpression across multiple cancer types promotes dysregulated tyrosine kinase activation and results in tumor progression and unchecked malignance with exciting potential for targeted therapies in solid tumors. 3H-10000 is a novel vedotin antibody-drug conjugate (ADC) comprising a specific anti-FGFR2b human monoclonal antibody conjugated to the cytotoxic payload monomethyl auristatin E (MMAE) via a protease-cleavable maleimidocaproyl valine citrulline (mc-vc) linker. FGFR2b mAb as carrier, selectively target and deliver ADC (3H-10000) molecules to tumors, reducing systemic toxicity and enhancing therapeutic efficacy; the linker is stable in circulation, effectively cleaves and releases payload inside tumor cells, reducing off-target toxicity, and exerts bystander effect to address tumor heterogeneity; the applied payload is cytotoxic and highly efficient. In vitro, 3H-10000 demonstrated FGFR2b-specific binding to cells, efficient internalization, FGFR2b-expression-dependent cytotoxicity, and bystander effects. Pharmacokinetic analyses in mice bearing FGFR2-positive SNU-16 tumors showed that MMAE, the payload of 3H-10000 achieves tumor exposure that is more than 400-fold higher than plasma exposure. Efficacy studies demonstrated robust and sustained antitumor activity in gastric carcinoma and sqNSCLC xenograft mouse models (CDX 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 LB268.
Gao et al. (2026) studied this question.