Updated efficacy results of ASKB589 combined with CAPOX and PD-1 inhibitor as first-line treatment for metastatic gastric/gastro-esophageal junction (G/GEJ) adenocarcinoma from a phase Ib/II study.
Authors: Zhi Peng, Hong Zhu, Jufeng Wang, Luwei Han, Jing Chen, Jianfeng Lu, Lin Shen
Journal: Journal of Clinical Oncology (2025)

454 Background: ASKB589 is a non-fucosylated fully human IgG1 monoclonal antibody that binds CLDN18.2 with high affinity, specificity, and improved ADCC and CDC activities. Previous findings indicated that ASKB589 exhibited a well-tolerated safety profile at doses up to 20 mg/kg and demonstrated promising antitumor effects. A dose of 6 mg/kg has been selected for further evaluation. Here, we present the updated data from dose expansion part in NCT05632939 study. Methods: This phase 1b/2 study was consisted of dose-escalation part and dose-expansion part. The expansion part aimed to assess the safety and efficacy of ASKB589 combined with CAPOX plus a PD-1 inhibitor as the initial treatment for advanced G/GEJ cancer with CLDN18.2 positive, regardless of PD-L1 expression. CLDN18.2 and PD-L1 expression were evaluated through IHC analysis using clone DS-3 and clone E1L3N at a central lab. All pts were given ASKB589 intravenously at a dosage of 6 mg/kg. Responses were assessed by RECIST 1.1 every 6 weeks. Adverse events were graded using CTCAE v5.0. Results: As of July 29, 2024, 49 evaluable pts with CLDN18.2 M/H expressions (≥2+ membrane staining intensity in ≥40% of tumor cells) regardless of PD-L1 CPS score. Forty pts (81.6%) achieved a partial or complete response, with a confirmed objective response rate (cORR) of 73.5% (95%CI: 58.9, 85.1). The median duration of response was 11.14 months (6.93, NE). Three subjects underwent surgical treatment as a result of tumor reduction following treatment. All 49 pts achieved SD or better with a disease control rate of 100%. cORR was 76.2% and 74.1% in the CPS&lt;1 and CPS&lt;5 groups, respectively. Of all treated pts (N=50), PFS rate at 9 months was 58.1% (95% CI: 42.2, 71.0) and OS rate at 12 months was 77.1% (95% CI: 61.2, 87.2). Mature PFS and OS data will be reported at the time of the conference. The safety profile of the triplet is generally consistent with the safety data of ASB589 plus CAPOX combination in first-line G/GEJ cancer pts presented previously, which was mainly characterized by manageable on-target-off-tumor effects, including hypoalbuminemia, nausea, and vomiting. Conclusions: The combination of ASKB589 with CAPOX and a PD-1 inhibitor as the initial treatment for pts with G/GEJ cancer was well tolerated with no unexpected safety signals. It has shown a high confirmed ORR, 100% disease control, deep and durable antitumor activity, regardless of PD-L1 expression levels. A phase 3 study of the triple regimen for the 1L G/GEJ cancer is actively enrolling pts in China. Clinical trial information: NCT05632939 . cORR based on CLDN18.2 and PD-L1 expression. n/N (%) PD-L1CPS&lt;1 PD-L1CPS 1-5 PD-L1 CPS≥5 Total CLDN18.2 M&amp;HcORR 16/21(76.2%) 7/10 (70.0%) 13/18 (72.2%) 36/49 (73.5%) CLDN18.2 Moderate cORR 2/3(66.7%) 0/1(0.0%) 6/9(66.7%) 8/13(61.5%) CLDN18.2 High cORR 14/18(77.8%) 7/9(77.8%) 7/9(77.8%) 28/36(77.8%)