Low Anticoagulant Herapin Derivative Linked to Complete Responses for AML

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CX-01 added to standard of care was well-tolerated and did not increase incidence of bleeding in patients >59 years old.

New data from the American Society of Clinical Oncology (ASCO) 2021 Meeting highlights the potential efficacy of CX-01, a low anticoagulant herapin derivative, for the treatment of acute myeloid leukemia (AML) in older adults.

CX-01 is a relatively novel agent “that retains heparin’s ability to alter the activity of the CXCL12/CXCR4 axis, P-selectin, extracellular histones, and Platelet Factor 4.” In 2018, the US Food and Drug Administration (FDA) granted it fast track designation for patients over 60 years of age.

In this current randomized, dose-finding study, a team of investigators, led by Tibor Kovacsovics, MD, of Huntsman Cancer Institute, evaluated the efficacy of CX-01 in combination with standard of care. This trial comes in the wake of recent findings from a pilot study showing that the combination therapy was associated with a complete remission (CR) rate of 92%.

As such, they enrolled and evaluated a total of 66 patients >59 years old. Patients were randomized to idarubicin and cytarabine on a 7+3 schedule (Group 1), 7+3 plus CX-01 0.125 mg/kg/hour (Group 2), or 7+3 plus CX-01 0.25 mg/kg/hour (Group 3).

Patients who achieved CR received consolidation therapy, which included ≤3 cycles of cytarabine 1000 mg/m2 every 12 hours on Days 1, 3, 5 without or with the same dose of CX-01 in all 3 groups, respectively.

CX-01 was administered as a continuous infusion after a 4 mg/kg bolus until patients completed chemotherapy.

Data presented at the conference represented all evaluable patients rather than an intent to treat population.

“The composite CR rate (CR + CRi) was highest for patients in Group 3 with 89% patients achieving a composite CR as compared to 58% and 50% in Groups 1 and 2, respectively,” Kovacsovics and colleagues reported.

They also drew attention to Kaplan-Meier curves, which indicated a statistically significant improvement in event free survival (EFS) (P = .019) as well as a non-significant trend (P = 0.10) to improvement in overall survival in Group 3 versus Group 1.

The standard of care and CX-01 low-dose cohorts demonstrated comparable results in terms of EFS and overall survival.

Further, the low anticoagulant herapin derivative was considered well-tolerated for all patients, and there were no increased incidences of bleeding in the two CX-01 treatment groups.

“The encouraging CR rate and EFS in elderly fit patients with newly diagnosed AML suggests that CX-01 may potentiate the efficacy of standard AML induction therapy,” they wrote. “A randomized study to confirm these findings with the higher dose of CX-01 is warranted.”

The study, “A randomized phase II trial of CX-01 with standard therapy in elderly patients with acute myeloid leukemia (AML),” was presented at ASCO 2021.