Abstract Background: Sialyl-Thomsen-nouveau(STn)antigen is a truncated O-glycan generated by early sialylation of the Tn antigen. While with limited expression in normal tissues, STn is overexpressed in numerous human carcinomas, including ovarian, breast, bladder, cervical, colon, pancreatic and lung cancers. LM-338, a STn-targeted antibody-drug conjugate (ADC), is comprised of a humanized monoclonal antibody (LM-138) conjugated to a topoisomerase I inhibitor via a cleavable linker, with a drug-antibody ratio of 4. Methods: Target binding activity of LM-338 was assessed by flow cytometry. Internalization was evaluated using a pH-sensitive dye. Binding specificity was evaluated using glycan array. Cytotoxic and bystander effects were measured using CellTiter-Glo luminescent cell viability assay. In vivo anti-tumor activity of LM-338 was examined in several STn-positive cell line-derived xenograft (CDX) and patient-derived xenograft (PDX) models. Immunohistochemistry was used to assess STn expression in tumor tissues. Toxicity was evaluated inrepeated-dose toxicity study in rhesus monkeys. Results: LM-338 showed high binding activity and specificity to STn with minimal cross-reactivity to sialyl-T-antigen. LM-338 bound to and was internalized by STn-positive tumor cells in a dose-dependent manner, resulting in potent cytotoxic and bystander effects in vitro. In vivo, LM-338 (3 or 6 mg/kg) induced significan tumor growth inhibition or regression across multiple CDX and PDX models (ovarian, colorectal and lung cancers), with superior efficacy as compared to a DXd-conjugated comparator. LM-338 was well tolerated in non-human primates at dosed up to 60 mg/kg. Conclusion: LM-338, an anti-STn ADC, demonstrated potent anti-tumor activityacross several solid tumor models with favorable preclinical tolerability. These findings support further clinical development of LM-338 for patients with STn-expressingmalignancies. Disclosure: The study was funded by LaNova Medicines Limited, China. Citation Format: Jin Li, Junwei Yang, Yuan Li, Te Du, Xia Qin, Da Fei, Lei Shi, Wei Cao. Preclinical evaluation of LM-338: An innovative anti-STn antibody drug conjugate for solid tumors abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 5636.
Li et al. (Fri,) studied this question.