Palleon's E-602 Shows Promise in Combination with Cemiplimab for Anti-PD-(L)1 Resistant Solid Tumors
核心洞察
Palleon Pharmaceuticals (搜索) presented Phase 1/2 GLIMMER-01 trial results of E-602 with cemiplimab in patients with PD-(L)1 (搜索)-resistant solid tumors.
The combination therapy was well-tolerated, with no dose-limiting toxicities observed in the studied patient cohort.
Patients with tumor hypersialylation showed better clinical outcomes, including a partial response in melanoma (搜索) and disease stabilization in others.
Palleon Pharmaceuticals (搜索) announced results from its Phase 1/2 GLIMMER-01 trial, evaluating E-602, a first-in-class human sialidase enzyme therapeutic, in combination with cemiplimab (Libtayo®), a PD-1 (搜索) inhibitor, for patients with solid tumors resistant to PD-(L)1 (搜索) therapy. The data, presented at the Society for Immunotherapy of Cancer (SITC) Annual Meeting, suggest that the combination is well-tolerated and shows potential efficacy in patients with tumor hypersialylation.
The GLIMMER-01 trial included 21 patients with melanoma (搜索), non-small cell lung cancer (搜索), and esophagogastric junction cancer (搜索), all defined as resistant to anti-PD(L)-1 therapies per SITC consensus. Patients were assessed for tumor sialoglycan levels, categorizing them as having hypersialylation or not. The study's primary focus was on safety and preliminary efficacy signals.
The combination of E-602 and cemiplimab was generally well-tolerated, with no dose-limiting toxicities observed. Notably, patients exhibiting tumor hypersialylation trended towards improved clinical outcomes compared to those without. One patient with anti-PD-1 (搜索) resistant melanoma (搜索) achieved a confirmed partial response, and six other patients experienced disease stabilization. Conversely, all patients lacking hypersialylation experienced disease progression.
Glycan Editing Mechanism
Paired tumor biopsies from patients with hypersialylation revealed tumor desialylation and immune modulation. However, the tumor desialylation effect lasted only 2-3 days with weekly dosing. These findings offer initial proof of mechanism for glycan editing as a novel therapeutic strategy to modulate the immune system.
Li Peng, Ph.D., Chief Scientific Officer of Palleon Pharmaceuticals (搜索), stated, "The proof of mechanism and antitumor responses observed with E-602 as a combination therapy for patients with solid tumors further validate the therapeutic potential of targeting glyco-immunology to regulate the immune response in treating cancer and autoimmune diseases."
Future Directions
Palleon is developing next-generation EAGLE molecules with a longer half-life sialidase and a tumor-targeting moiety to address the unmet needs of cancer patients. Jim Broderick, M.D., CEO and Founder of Palleon, added that E-602 represents a new class of therapeutics designed to modulate the immune system by targeting glyco-immunology.