On September 14, 2016 GlycoMimetics, Inc. (NASDAQ: GLYC) reported it has dosed its first patient in a Phase 1 clinical trial of its novel E-selectin antagonist, GMI-1271, combined with bortezomib-based chemotherapy, for multiple myeloma (Press release, GlycoMimetics, SEP 14, 2016, View Source [SID:SID1234515148]). The trial marks a second application for GMI-1271, which already is undergoing clinical study as a potential treatment for acute myeloid leukemia (AML). Schedule your 30 min Free 1stOncology Demo! The newly initiated multi-center, open-label dose escalation trial, which has begun in Ireland, will measure the efficacy, safety and pharmacokinetics of GMI-1271 in combination with chemotherapy among patients who have been diagnosed with multiple myeloma and have not responded well to standard chemotherapy. The company anticipates enrolling 24 participants in the trial.
Discover why more than 1,500 members use 1stOncology™ to excel in:
Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing
Schedule Your 30 min Free Demo!
"This new clinical trial provides an opportunity to evaluate GMI-1271’s ability to treat hematological cancers beyond AML," said Dr. John Quinn, Consultant Haematologist, Beaumont Hospital, Dublin, Ireland. "Preclinical studies showed promise for E-selectin antagonists against other types of cancers, so this pilot study in multiple myeloma may determine if GMI-1271 may become part of a bortezomib rescue treatment for patients not responding to standard regimens." Beaumont Hospital is one of a number of Blood Cancer Network Ireland (BCNI) sites participating in this study.
In preclinical studies, mice with multiple myeloma that were treated with GMI-1271 and bortezomib showed improvement in survival compared to those treated with bortezomib alone. Furthermore, in mice with myeloma resistant to treatment with bortezomib, addition of GMI-1271 restored bortezomib sensitivity. In addition, blood samples from individuals with multiple myeloma showed increases in cell surface expression of E-selectin carbohydrate ligands when cancer had relapsed, indicating E-selectin as a promising target for reducing drug resistance in certain groups of patients who have the disease.
Multiple myeloma is a neoplastic proliferation of plasma cells derived from bone marrow. The cells ultimately infiltrate a number of organs and lead to bone marrow destruction and failure. It is the most common tumor in the bone and the second most-common blood cancer in the US and Europe. According to EU data from 2012, 39,000 new diagnoses were made for multiple myeloma, and 24,000 people died from the disease there. Most patients currently ultimately relapse from chemotherapy, and the disease is not considered curable using current approaches.
In the Phase 1 study, participants will include individuals who have been diagnosed with multiple myeloma and undergone bortezomib-based therapy with inadequate responses. The patients will receive one of four doses of GMI-1271 in combination with bortezomib, intravenously concurrently with bortezomib treatment. They will be followed after treatment to measure safety endpoints and efficacy.
About GMI-1271
GMI-1271 is designed to block E-selectin (an adhesion molecule on cells in the bone marrow) from binding with blood cancer cells as a targeted approach to disrupting well-established mechanisms of leukemic cell resistance within the bone marrow microenvironment. Preclinical research points to the drug’s potential role in moving cancerous cells out of the protective environment of the bone marrow where they hide and escape the effects of chemotherapy. In preclinical studies using animal models of AML, the results of which were presented at meetings of the American Society of Hematology (ASH) (Free ASH Whitepaper), GMI-1271 was also associated with a reduction of chemotherapy-induced neutropenia and chemotherapy-induced mucositis.