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.

• DOI: 10.1200/jco.2024.42.16_suppl.3037
• Publication Date: 2024-07-02T00:51:20Z
• Authors: Xianjun Yu; Jian Zhang; Andrea Tazbirkova; Jianwei Yang; Jinbo Yue; Yuping Sun; Yueyin Pan; Meili Sun; Yanru Qin; Lin Shen; Rongfeng Song; Jian Ruan; Aiping Zhou; Yiping Mou; Zimin Liu; Zhenyang Liu; Yongchang Zhang; Michelle Morris; Morteza Aghmesheh; Hui Zhou
• Keywords: Conjugate; Biliary Tract Cancer; Antibody-drug conjugate

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