758 GLIMMER-01: phase 1/2 trial of a first-in-class bi-sialidase (E-602) in combination with cemiplimab in patients with PD-(L)1-resistant solid tumors

作者：Manish Sharma, Melissa L. Johnson, Igor Puzanov, Mario Sznol, Meredith McKean, Justin F. Gainor, Alexander I. Spira, Brian S. Henick, Anthony W. Tolcher, Christopher T. Chen, Anthony B. El-Khoueiry, James Broderick, Peng Li, Jenny Che, Lizhi Cao, Dawn Wilson, Deanne Lathers, Christine E. Horak, David Feltquate, Jason J. Luke · 发表于：Regular and Young Investigator Award Abstracts · 年份：2024 · DOI：10.1136/jitc-2024-sitc2024.0758 · 被引用次数：6 · 研究领域：Cancer Research and Treatments、Glycosylation and Glycoproteins Research、Peptidase Inhibition and Analysis

Background Tumor cell hypersialylation is immune suppressive and associated with poor outcomes in cancer patients. E-602 is a first-in-class fusion protein of engineered human sialidase (Neu2) and IgG1fusion that cleaves sialic acids from sialoglycans on immune and tumor cells, alleviating immune suppressive mechanisms. In Phase 1, E-602 monotherapy was tolerable at doses up to 30 mg/kg and achieved dose-dependent pharmacodynamic (PD) effects for up to 48 hours including changes in circulating immune cell desialylation and immune modulation. Here we share the safety, efficacy and tumor PD effects of E-602 in combination with cemiplimab (anti-PD-1). Methods The Combination Part of GLIMMER-01 (NCT05259696) evaluated the safety, pharmacokinetics (PK), PD and anti-tumor activity of weekly 20 mg/kg E-602 in combination with q3w 350 mg cemiplimab in I-O resistant cancer patients. Tumor biopsies were collected prior to first treatment and after 4–5 E-602 infusions and assessed by immunohistochemistry to measure tumor desialylation using HYDRA , proprietary reagents recognizing Siglec-engaging sialoglycans, and immune modulation. Results As of April 2024, 21 anti-PD(L)-1-resistant melanoma, NSCLC and EGJ patients (8, 12, and 1, respectively) were treated with at least one dose of E-602-cemiplimab. The most frequent treatment-related AEs were infusion related reactions (any grade: 38%; ≥ grade 3: 4.7%), which were clinically manageable. Partial response (PR) and stable disease (...