Efficacy and safety of XNW27011, a Claudin 18.2 targeting antibody drug conjugate with topoisomerase 1 inhibitor payload, in patients with Claudin 18.2 positive gastric/gastroesophageal junction cancer: Results from ongoing phase I/II study.

3034 Background: CLDN18.2 is a clinically validated target for cancer treatment. XNW27011 is a CLDN18.2 targeted ADC conjugated with a novel topoisomerase 1inhibitor (topo1i). Dose-escalation study of XNW27011 demonstrated favorable safety, pharmacokinetics, and promising preliminary efficacy in advanced solid tumors. Here we report the results of XNW27011 in CLDN18.2+ GC/GEJC pts from ongoing expansion cohorts. Methods: Pts with CLDN18.2+ (TC≥5%, IHC ≥ 2+), advanced/metastatic solid tumors progressed on standard therapy and an ECOG PS of 0-2 are eligible to be enrolled in dose expansion cohorts. Pts received XNW27011 iv infusion Q3W at doses of 2.4, 3.0 and 3.6 mg/kg. 1 st endpoint is ORR, 2 nd endpoints include safety, other efficacy parameters, PK, ADA, and correlation between CLDN18.2 expression and efficacy. Results: As of Dec 28 th , 2024, a total of 116 pts with CLDN18.2+ solid tumors including 84 GC/GEJC pts were enrolled in expansion cohorts at doses of 2.4 mg/kg, 3.0 mg/kg and 3.6 mg/kg, with median age of 59 years, median lines of prior treatment 2, 80.2% received checkpoint inhibitors and 18.6% topo1i-containing therapies. The most common any grade TEAE (≥ 20%) in all patients were nausea, vomiting, anemia, appetite ↓, WBC ↓, neutrophil ↓, asthenia, hypoalbuminemia, platelet ↓, body weight ↓, and hypokalemia. The most common ≥ G3 TEAEs (≥5%) were neutrophil ↓, WBC ↓, anemia, lymphocyte ↓, and asthenia. TEAEs leading to dose interruption at 2.4, 3.0 and 3.6 mg/kg were 15.2%, 26% and 60%, dose reduction 10.9%, 26%, and 65%, and dose discontinuation 10.9%, 8%, and 0%. 1 pt at 3.0 mg/kg experienced TEAE leading to death (pneumonia). Safety profile was consistent with that of dose escalation part. In the 84 GC/GEJC pts enrolled in dose expansion, 75 pts were evaluable with at least one post baseline scan. The BOR and DCR across dose groups were 46.7% and 88.0%, respectively. Efficacy in each dose group was summarized in the table below. The median follow up was 4.3M, 4.0M and 7.0M for 2.4, 3.0, and 3.6 mg/kg. Preliminary anti-tumor activity was also observed in pts who had prior CPI and topo 1i containing treatments, as well as in other CLDN18.2+ solid tumor pts. Conclusions: In the expansion cohorts,XNW27011 demonstrated promising anti-tumor activity and favorable safety profile in GC/GEJC pts with wide expression level of CLDN18.2.The results support further development of XNW27011 in CLDN18.2+ GC/GEJC. Clinical trial information: CTR20231735 . 2.4 mg/kgN=27 3.0 mg/kgN=30 3.6 mg/kgN=18 BOR, n (%) 7 (25.9%) 16 (53.3%) 12 (66.7%) PR (confirmed) 4 (14.8%) 9 (30%) 6 (33.3%) cPR Pending 2 (7.4%) 5 (16.6%) 3 (16.7%) DCR, n (%) 23 (85.2%) 27 (90.0%) 16 (88.9%)