Comprehensive Report on QLS-31905: A Novel CLDN18.2/CD3 Bispecific T-Cell Engager for Advanced Solid Tumors

Executive Summary

QLS-31905 is an investigational bispecific T-cell engager (BiTE) antibody developed by Qilu Pharmaceutical Co., Ltd., engineered to target two distinct proteins: Claudin 18.2 (CLDN18.2), a tumor-associated antigen, and CD3, a component of the T-cell receptor complex.[1] This dual-targeting mechanism is designed to physically link a patient's own cytotoxic T-cells to cancer cells expressing CLDN18.2, thereby inducing potent, targeted tumor cell lysis. The development of QLS-31905 is strategically positioned within a therapeutic landscape recently validated by the regulatory approval of zolbetuximab (Vyloy), the first-in-class monoclonal antibody targeting CLDN18.2.

The clinical development program for QLS-31905 is spearheaded by the Phase 1 monotherapy trial, NCT05278832, which has provided crucial proof-of-concept data in a heavily pre-treated population of patients with advanced solid tumors. Updated results presented at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting demonstrated encouraging anti-tumor activity. Among 33 evaluable CLDN18.2-positive patients, the objective response rate (ORR) was 18.2%, and the disease control rate (DCR) was a notable 87.9%. Efficacy was particularly pronounced in patients with pancreatic adenocarcinoma, who achieved an ORR of 25.0%.[3] These results are complemented by a manageable safety profile. A key concern for T-cell engaging therapies, Cytokine Release Syndrome (CRS), occurred in 21.5% of patients, but severe (Grade

≥3) events were infrequent (3.8%), and all cases were reversible. Critically, a maximum tolerated dose (MTD) was not reached, suggesting a favorable therapeutic window.[3]