GLIMMER-01 Beings Examination of E-602 Plus Cemiplimab in Advanced Cancers

The glyco-immune checkpoint inhibitor, E-602, in combination with cemiplimab (Libtayo) has been dosed in the first patient with an advanced cancer in the phase 2 GLIMMER-01 clinical trial (NCT05259696).¹

E-602 is the first agent in its class and proof of its mechanism was previously reported at the American Association for Cancer Research in the phase 1 portion of the study. Overall, E-602 was well-tolerated with no dose-limiting toxicities shown, according to findings from 40 patients treated with intravenous (IV) E-602 at 1 mg/kg and 30 mg/kg once weekly. Moreover, dose-dependent desialylation and immune system activation were achieved with the drug.²

"The ability of the field to study hypersiaylation of tumor and immune cells has opened a new field of glyco-immunobiology. E-602 represents the first glyco-immune checkpoint inhibitor and the early safety as well as translational immunology associated with the treatment in patients with advanced cancer is promising," Jason Luke, MD, FACP, associate professor of medicine in the Division of Hematology/Oncology and the director of the Cancer Immunotherapeutics Center within the UPMC Hillman Cancer Immunology and Immunotherapy Program told Targeted Oncology^TM.

In the open-label, single-arm, dose-escalation, and dose-expansion study, investigators aim to determine the safety, tolerability, pharmacokinetics, and antitumor of E-602 in combination with cemiplimab. To determine these measures, the primary end points to be assessed in phase 2 are overall response rate, duration of response, progression-free survival, and overall survival. Investigators will also evaluate the incidence adverse events (AEs) and serious Aes, maximum plasma concentration of E-602, area under the plasm concentration-time curve for the agent, and the number of patients with detectable anti-drug antibodies.³

Patients enrolled in the monotherapy arm will receive the recommended phase 2 dose (RP2D) of E-602, and those in the combination arm with receive the RP2D of E-602 and cemiplimab 350 mg via IV infusion, once every 3 weeks.

Those with advanced cancers, including relapsed or refractory melanoma, ovarian cancer, non–small cell lung cancer, colorectal cancer, pancreatic cancer, breast cancer, gastric/esophagogastric junction cancer, head and neck cancer, or urothelial cancer who progressed while being treated previously, are eligible to enroll in GLIMMER-01 given they have an ECOG performance status of 0 or 1, measurable disease, and adequate bone marrow, coagulation, renal function, and liver function, according to the study criteria.

Patients are excluded if have hypersensitivity to cemiplimab or a prior unresolved toxicity, a prior malignancy or other illness, or comorbidities that may interfere with study treatment. Prior receipt of idelalisib (Zydelig), surgery or treatment with another investigation drug, a vaccine with 14 days of study treatment, allogeneic tissue, or organ transplantation, or greater than 10 mg of oral prednisone daily or on systemic immunosuppressive therapy are grounds for exclusion from the study.

The study is actively recruiting patients with advanced cancers at sites in California, Connecticut, Michigan, New York, Oregon, Pennsylvania, Tennessee, and Texas.

_REFERENCES:

_{1. Palleon Pharmaceuticals announces first patient dosed with E-602 in combination with cemiplimab in GLIMMER-01 phase 1/2 clinical trial. News release. Palleon Pharmaceuticals. June 22, 2023. Accessed June 23, 2023. https://tinyurl.com/2sxzsrw6}

_{2. Luke JJ, Johnson M. Tolcher A, et al. Abstract CT034: GLIMMER-01: initial results from a phase 1 dose escalation trial of a first-in-class bi-sialidase (E-602) in solid tumors. Cancer Res. 2023;83(suppl 8): CT034. doi:10.1158/1538-7445.AM2023-CT034}

_{3. Glycan mediated immune regulation with a bi-sialidase fusion protein (GLIMMER-01) (GLIMMER-01). ClinciaTrials.gov. Updated February 17, 2023. Accessed June 23, 2023.https://classic.clinicaltrials.gov/ct2/show/NCT05259696}