Dr Luke on Initial Data From the GLIMMER-01 Trial of E-602 in Advanced Solid Tumors

Jason Luke, MD, FACP, associate professor of medicine, Division of Hematology/Oncology, director, Cancer Immunotherapeutic Center, Immunology and Immunotherapy Program, UPMC Hillman Cancer Center, discusses initial results from the phase 1 GLIMMER-01 trial (NCT05259696) of E-602 in advanced solid tumors.

E-602 is a first-in-class fusion protein consisting of an engineered human sialidase (Neu2) and a human IgG1 Fc region. Recently improved understanding of the impact of glycosylation patterns on tumor cell immunity provided the impetus for investigating this novel therapeutic class. E-602 was shown to successfully bolster immune function by augmenting T-cell activation in preclinical studies and demonstrated antitumor activity as a monotherapy in mouse models.

The first-in-human GLIMMER-01 study was designed to evaluate the safety, pharmacokinetics, pharmacodynamics, and antitumor activity of E-602 in patients with advanced solid tumors who no longer respond to standard-of-care therapeutics. Tumor types included ovarian cancer, melanoma, breast cancer, colorectal cancer, gastric cancer, pancreatic cancer, urothelial cancer, head and neck cancer, and non–small cell lung cancer (NSCLC). Intravenous E-602 was administered once a week to eligible patients in a modified 3+3 dose escalation. Dose levels ranged from 1 to 30 mg/kg.

Results from the dose-escalation portion of this study show that E-602 was safe and tolerable up to doses of 30mg/kg with no dose-limiting toxicities observed. Establishing the safety of a novel therapeutic modality is paramount in ensuring that patients will not be significantly hurt by the strategy, Luke says.

Additionally, the agent showed on-target immunological effects associated with improved outcomes in the peripheral blood. At higher dose levels, the agent showed sustained and biological meaningful levels of desialylation after treatment with E-601. Similar increases in desialylation were observed for CD4+ T cells, natural killer cells, and monocytes. However, these biomarker observations did not translate to definitive treatment responses in this patient population. Future investigations of E-602 in other populations may increase the chance of seeing these responses in clinic, Luke notes.

Based on these safety and preliminary efficacy data, the phase 2 portion of GLIMMER-01 will proceed as planned. This portion will evaluate the clinical activity of single-agent E-602 in patients with immune checkpoint inhibitor–resistant NSCLC and melanoma. Biomarker and translational investigations of the agent's effect on tumor and immune cells are also planned. These studies will confirm whether the pharmacodynamic effect of E-602 on certain immune subsets in peripheral blood is consistent with its activity preclinical mouse models.