GlycoMimetics Doses First Patient in Phase 1 Clinical Trial of Drug Candidate GMI-1271 for Multiple Myeloma
Trial to test candidate for second blood cancer type among patients responding poorly to standard therapy
The newly initiated multi-center, open-label dose escalation trial,
which has begun in
"This new clinical trial provides an opportunity to evaluate GMI-1271's
ability to treat hematological cancers beyond AML," said Dr.
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
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.
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), GMI-1271 was also associated with a reduction of chemotherapy-induced neutropenia and chemotherapy-induced mucositis.
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