Safety and efficacy of IBI343 (anti-claudin18.2 antibody-drug conjugate) in patients with advanced pancreatic ductal adenocarcinoma or biliary tract cancer: Preliminary results from a phase 1 study.

3037 Background: Prognosis for advanced pancreatic ductal adenocarcinoma (PDAC) and biliary tract cancer (BTC) remains poor, with limited treatment options available. Expression of claudin18.2 (CLDN18.2) has emerged as a potential target for anti-cancer treatment. Herein, we report preliminary safety and efficacy results of IBI343, an antibody-drug conjugate (ADC) consisting of anti-CLDN18.2 monoclonal antibody conjugated to exatecan (topoisomerase I inhibitor), in patients (pts) with advanced PDAC or BTC in a phase 1 study. Methods: Eligible pts who failed or were intolerant to standard treatment were enrolled. IBI343 were intravenously administered at 6 mg/kg or 8 mg/kg Q3W. In dose escalation, pts were enrolled regardless of CLDN18.2 expression. In dose expansion, pts were required to have CLDN18.2 expression ≥40% (1+/2+/3+ staining intensity by immunohistochemistry). Primary endpoint was safety. Secondary endpoints included objective response rate (ORR), disease control rate (DCR), duration of response (DoR) and progression free survival (PFS) assessed by investigator per RECIST v1.1. Results: As of December 19, 2023, 35 pts (1 pt in dose escalation and 34 pts in dose expansion) were enrolled from China and Australia (males: 57.1%, median age: 58.0 years, ECOG PS 1: 71.4%, stage IV: 91.4%, median lines of prior treatment: 2) including 28 PDAC pts and 7 BTC pts. Pts received IBI343 at 6 mg/kg (n=17) or 8 mg/kg (n=18). Median duration of treatment was 7.0 weeks (range: 3.0-23.6) with 23 (65.7%) pts still on treatment. In all pts, treatment-related adverse events (TRAEs) occurred in 28 (80.0%) pts including grade ≥3 TRAEs in 9 (25.7%) pts. Common TRAEs (≥20%) were anemia (42.9%), neutrophil count decreased (28.6%), nausea (25.7%), vomiting (25.7%) and white blood cell count decreased (22.9%). Serious TRAEs occurred in 4 (11.4%) pts. TRAEs leading to dose interruption and treatment discontinuation occurred in 7 (20.0%) pts and 1 (2.9%) pt respectively. No TRAE led to death. Safety profiles of IBI343 in PDAC and BTC were comparable with the whole study cohort and no new safety signal was observed. As of January 15, 2024, 25 pts at 6 mg/kg and 8 mg/kg were efficacy evaluable. Partial response (PR) was observed in 7 pts (5 PDAC and 2 BTC). The ORR was 28.0% (95%CI: 12.1-49.4) and DCR was 80.0% (95%CI: 59.3-93.2). In evaluable pts at 6 mg/kg with CLDN18.2 expression ≥60% (1+/2+/3+, n=13), 5 pts had PR with ORR of 38.5% (95%CI: 13.9-68.4) and DCR of 84.6% (95%CI: 54.6-98.1). Among 10 PDAC pts in this subgroup, ORR was 40% (95%CI: 12.2-73.8). DoR and PFS data were immature. More updated data on safety and efficacy will be presented at the meeting. Conclusions: IBI343 was well tolerated with favorable safety profiles and encouraging efficacy in CLDN18.2-positive PDAC and BTC. Clinical trial information: NCT05458219 .