First in human phase I study of TQB2103, a Claudin18.2 (CLDN18.2) targeted antibody-drug conjugate (ADC), in patients with advanced solid tumors.

3026 Background: Claudin18.2 is a promising target for CLDN18.2-expressing cancers such as gastric and pancreatic cancers. TQB2103 is a novel ADC comprised of a humanized anti-CLDN18.2 IgG1 monoclonal antibody, a cleavable linker and topoisomerase I inhibitor, with a drug-to-antibody-ratio (DAR) of 8. Methods: This is a multicenter, first-in-human study of TQB2103 in patients (pts) with previously treated advanced solid tumors. This study comprised of a dose escalation part in patients regardless of Claudin18.2 expression level and a dose expansion part in patients specified by CLDN18.2 positive expression. The primary objectives were to assess safety and tolerability and determine the recommended phase 2 dose. Secondary objectives were to assess the pharmacokinetics and preliminary anti-tumor activity. Results: As of December 16 2024, 59 pts were enrolled to receive TQB2103 intravenously every 3 weeks at 7 dose level (range from 0.5 to 6.0mg/kg). One patient experienced dose-limiting toxicity (DLT) of grade 3 transaminase elevation at 0.5mg/kg which might also be related to the comorbidity of choledocholithiasis. Fifty-six (94.9%) patients experienced at least one treatment-related adverse event (TRAE). The most frequent TRAEs were nausea (72.9%), vomiting (64.4%), appetite decreased (57.6%), hypoalbuminemia (49.2%), anemia (49.2%), white blood cell decreased (44.1%), and asthenia (44.1%). The most frequent grade ≥3 TRAEs were anemia (11.9%) and neutrophil count decreased (10.2%). Most of AEs were grade 1 or grade 2 and manageable. Among the 30 response evaluable pts with CLDN18.2 expression, the ORR and DCR were 20% and 76.7%, respectively. Shrinkage of the target lesions occurred in 17(56.7%) patients. In patients with CLDN18.2 moderate to high expression, the ORR was 42.9% of gastric cancer at 5mg/kg. Surprisingly, all of 3 response-evaluable biliary tract cancer had shrinkage of the target lesions at the first assessment, and 1/3 achieved partial response. Conclusions: TQB2103 demonstrated encouraging anti-tumor activity in CLDN18.2 positive solid tumors, with a favorable safety profile. The findings support further development of TQB2103 monotherapy or in combination with other anti-cancer therapies. Clinical trial information: NCT05867563 .