CELL INTELLIGENCE · 肿瘤细胞治疗研究

Pegenzileukin (SAR444245) is a pegylated recombinant human IL-2 variant designed to expand effector T cells and NK cells without stimulating regulatory T cells. This study evaluated pegenzileukin with pembrolizumab or cetuximab for treating advanced gastrointestinal cancers. A total of 138 patients with advanced gastric cancer (GC), colorectal carcinoma, esophageal squamous cell carcinoma (ESCC), and hepatocellular carcinoma (HCC) were enrolled across seven cohorts in this phase 2 study. Patients received pegenzileukin (24 µg/kg every 3 weeks [Q3W]) with pembrolizumab (200 mg Q3W) or cetuximab (initially 400 mg/m 2 and then 250 mg/m 2 weekly). The primary endpoint was the objective response rate (ORR). The secondary endpoints were time to response, response duration, clinical benefit rate, progression-free survival (PFS), and safety. Exploratory biomarker analyses assessed immune cell expansion and cytokine levels. The ORR varied across the cohorts, with the highest in ESCC cohort (1/5; 20.0%) and the lowest in GC Cohort 2 and the HCC cohort (1/19; 5.3% and 1/20; 5.0%, respectively). The median PFS was consistent across the cohorts (1.9-2.1 months). The most common treatment-emergent adverse events were asthenia (Pegenzileukin + pembrolizumab) and infusion-related reactions (Pegenzileukin + cetuximab). The biomarker analyses demonstrated robust expansion of CD8 + T cells, CD8 + Ki67 + T cells, NK cells, and NK Ki67 + cells without significant modulation of regulatory T cells. Pegenzileukin with pembrolizumab or cetuximab demonstrated limited efficacy, with a manageable safety profile in advanced GI cancers. The biomarker data supported the mechanism of action involving the upregulation of CD8 + T cells and NK cells. ClinicalTrials.gov Identifier: NCT05104567.