Qilu Pharmaceutical's CDH6-Targeting ADC QLS5133 Granted IND Approval in China for Advanced Solid Tumors

The official website of the Center for Drug Evaluation (CDE) of the China National Medical Products Administration (NMPA) has recently announced that the investigational new drug, QLS5133 Injection, submitted by Qilu Pharmaceutical Co., Ltd., has been approved for clinical trials. It is intended to be developed for the treatment of advanced solid tumors. Public information indicates that this is aAntibody-Drug Conjugates (ADC) Targeting CDH6, this is the first time that the product has been approved for clinical use in China.

Screenshot source: CDEOfficial Website

Cadherin-6 (CDH6), a member of the cadherin family, is expressed on the basolateral membrane of epithelial cells and mediates calcium-dependent cell-cell adhesion. Although the function of CDH6 has not been fully elucidated, it is thought to be associated with epithelial-mesenchymal transition (EMT) and metastasis during tumor progression. CDH6 is upregulated in various cancers, including ovarian cancer, renal cell carcinoma, and thyroid cancer, while its expression in normal tissues is limited. Moreover, after binding with an antibody, the ADC complex is rapidly internalized. Therefore, CDH6 is considered highly suitable as an ADC target.

Public information shows that QLS5133 is based on Qilu Pharmaceutical's independently developed novel topoisomerase 1 (TOPO 1) inhibitor platform, obtained through site-specific conjugation technology with a DAR value of 8. Its payload, QLS6916, exhibits nanomolar-level activity in various cancer cell lines.

At the 2025 AACR Annual Meeting, Qilu Pharmaceutical Co., Ltd. presented the preclinical study results of QLS5133 for solid tumors. The study showed that in CDH6-expressing human tumor xenograft models, such as ovarian cancer and renal cell carcinoma, QLS5133 treatment induced significant tumor regression. Even in CDX models with extremely low and highly heterogeneous CDH6 expression, QLS5133 still demonstrated robust efficacy. In preclinical models, QLS5133 achieved sustained remission in a case resistant to a FRα ADC, suggesting its potential as a later-line treatment option after the failure of prior therapies. At a single dose of 80 mg/kg in cynomolgus monkeys, QLS5133 exhibited significantly reduced hematological toxicity compared to a similar investigational product (with notably less impact on platelets, white blood cells, and neutrophils) and caused milder weight loss. Additionally, QLS5133 displayed superior pharmacokinetic properties in cynomolgus monkeys: a longer half-life of the intact ADC, slower systemic clearance, and maintenance of DAR retention over 21 days.

Researchers believe that QLS5133 exhibits excellent efficacy, good tolerability, and favorable PK characteristics, supporting its potential as a new drug to address the unmet clinical needs of patients with CDH6 heterogeneously expressed cancers.

[2]2881 / 20 - QLS5133-a novel CDH6-targeting antibody-drug-conjugate for solid tumors. From https://www.abstractsonline.com/pp8/#!/20273/presentation/3210