Vibecotamab Treatment at Dose-Optimized Schedule Shows Promise Among Patients With R/R AML

According to findings from a phase 1 trial published in Blood Advances, vibecotamab, a humanized bispecific antibody, administered at a dose-optimized schedule, demonstrated safety and tolerability among patients with relapsed/refractory (R/R) acute myeloid leukemia (AML). 

Farhad Ravandi, MD, The University of Texas MD Anderson Cancer Center, Houston, Texas, and coauthors explained that in the AML treatment landscape, “previous trials using cytotoxic agents were largely unable to improve outcomes significantly, but advancements in molecularly targeted agents have improved outcomes in some patient subsets.” 

They added, “Vibecotamab in CD123-expressing malignancies has shown potent dose-dependent killing of CD123+ tumor cells in vitro and in vivo.” In this trial, the study authors aimed to further assess the efficacy and safety of vibecotamab as a targeted monotherapy for AML. The primary end point was safety and the identification of a maximum tolerated dose/recommended dose among this population of patients.

A total of 120 patients with primary or secondary, relapsed or refractory AML, B-cell acute lymphocytic leukemia, blastic plasmacytoid dendritic cell neoplasm (BPDCN), or chronic myeloid leukemia (CML) in the blast phase, with no available therapy, were enrolled and administered vibecotamab. Safety, pharmacokinetics, and pharmacodynamics were measured. 

Results indicated that the recommended phase 2 dose of vibecotamab consisted of 3 step-up doses in week 1, which was correlated with a reduction in cytokine response syndrome (CRS), followed by weekly dosing. A total of 16 out of 120 patients experienced 1 or more treatment-emergent adverse events, the most common being CRS, which occurred in 59.2% of patients. CRS was managed with premedication and was primarily grade 2 or lower. 

Among the 111 patients with CD123-expressing AML eligible for efficacy assessment, 9% (n = 10) achieved an overall response of morphologic leukemia-free state or better, with an overall objective response rate of 9%. Response was only experienced among patients who received a target dose of 0.75 μg/kg or higher (n = 87), and the efficacy-evaluable overall response rate was 11.5%. Patients who had a response were more likely to have lower baseline blast counts in the blood and bone marrow (< 25%). 

The study authors concluded, “Dose optimization of the vibecotamab schedule resulted in a [recommended phase 2 dose] with an acceptable and tolerable safety profile in patients with relapsed/refractory AML.”

“Every-other-day step-up dosing was remarkably effective in suppressing CRS; further dose exploration could address whether even more aggressive step-up dosing would still be tolerable every 48 hours, and thereby achieve higher and earlier efficacious dose levels in the above recommended populations,” they added. 

Source: 

Ravandi F, Bashey A, Foran J, et al. Phase 1 study of vibecotamab identifies an optimized dose for treatment of relapsed/refractory acute myeloid leukemia. Blood Adv. Published online: October 26, 2023. doi: 10.1182/bloodadvances.2023010956