New Clinical Trial to Evaluate GPC-100 for the Treatment of AML

Exicure, Inc. plans to commence a clinical trial for GPC-100 (burixafor), a small molecule CXCR4 inhibitor, to treat acute myeloid leukemia (AML).¹

Taigen, the original developer of the drug, previously conducted a phase 1 chemosensitization study of GPC-100 in combination with fludarabine and cytarabine for 15 patients with relapsed or refractory AML.¹

According to preclinical data presented at the 66th American Society of Hematology Annual Meeting & Exposition by Pamela Becker, MD, PhD, of the City of Hope, combined blockade of CXCR4 with GPC-100 and the beta-2 adrenergic receptor led to improved chemotherapy response in patients.¹

Specifically, combining GPC-100 and the beta blocker propranolol with cytarabine chemotherapy increased drug sensitivity—shown by reduced IC50 by at least 4 to 10 fold and above—compared with cytarabine alone.¹

“The potential impact of CXCR4 inhibitors is that they may improve leukemia cell killing by releasing the cells from the protected marrow microenvironment. Ours was an in vitro study, so this drug would need to be evaluated in a clinical trial to ascertain whether there would be improvement in patient outcomes,” Dr. Becker told Blood Cancers Today.

The authors further explored the role of beta-blockers in AML through a retrospective review of a clinical trial on ulocuplumab in AML, which showed that 76.9% of patients who received non-selective beta-blockers with ADRB2 blocker activity achieved complete remission or complete Remission with incomplete count recovery as compared to 35.7% of patients who did not receive beta blockers.²

“These studies support further investigation of whether simultaneous blockade of CXCR4 and ADRB2 may potentiate chemotherapy response in AML, perhaps by disrupting microenvironment mediated chemotherapy protection,” wrote Dr. Becker and colleagues.²

GPC-100 is also being evaluated in an ongoing phase 2 trial in patients with multiple myeloma undergoing autologous hematopoietic stem cell transplant, with results expected in late 2025.¹

References

1. Exicure, Inc. (Nasdaq: XCUR) Announces Their Next Step in Planning for a New Clinical Trial in Acute Myeloid Leukemia (AML). Exicure, Inc. News Release. April 11, 2025. Accessed April 15, 2025. https://www.businesswire.com/news/home/20250411634017/en/Exicure-Inc.-Nasdaq-XCUR-Announces-Their-Next-Step-in-Planning-for-a-New-Clinical-Trial-in-Acute-Myeloid-Leukemia-AML
2. Tang Y, Braun A, von Behren Z, et al. Combined CXCR-4 inhibition with novel agent GPC-100 (burixafor) and beta 2 adrenergic receptor blockade enhances cytarabine response for acute myeloid leukemia blasts on stroma. Abstract 2758. Presented at: 66th American Society of Hematology Annual Meeting & Exposition; December 7-10, 2024; San Diego, CA.