Study Assessing Vibecotamab in MRD+ AML and MDS/CMML After Hypomethylating Agents

A phase 2 study (NCT05285813) is evaluating a CD3-CD123 bispecific T-cell engaging antibody vibecotamabin patients with minimal residual disease-positive acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) after hypomethylating agents (HMA) have failed.

An overview of the trial and study design were presented at the American Society of Clinical Oncology (ASCO) 2023 Annual Meeting, held June 2-6, in Chicago, Illinois, by Nicholas J. Short, MD, assistant professor, department of leukemia, The University of Texas MD Anderson Cancer Center.

“Outcomes of patients with MRD+ AML are poor... There are no current approved MRD-directed therapeutics for AML... Patients with higher risk MDS or chronic myelomonocytic leukemia (CMML) after HMA failure also have poor outcomes. There is no standard of care for MDS/CMML after HMA failure,” Short and colleagues wrote in their poster.

The study is enrolling patients in 2 cohorts, 1 for patients with MRD+ AML and 1 for patients with MDS/CMML after HMA failure. Patients that have received prior treatment with anti-CD123-directed therapy, have clinically significant organ dysfunction, or that are expected to be able to receive stem cell transplantation in the next 30 days will be excluded from the study.

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Participants will receive up to 4 cycles of intravenous vibecotamab. During the first cycle, patients will receive 0.43 µg/kg on day 1, 0.75 µg/kg on day 3, 1.1 µg/kg on day 5, and 1.7µg/kg on days 8, 15, and 22. During cycles 2 through 4, pateints will receive 1.7 µg/kg on days 1, 8, 15, and 22.

The study is primarily evaluating the rate of MRD negativity after 4 cycles of vibecotamab, with a goal of 50%. In the cohort of patients with MDS/CMML after HMA, the study aims to determine the overall response rate after 4 cycles with a goal of 30%. Secondary objectives include assessing other efficacy endpoints, including remission duration, duration of MRD response (in the AML MRD arm), rate of complete response (MDS arm), relapse-free survival and overall survival. Safety of vibecotamab in both arms is also a secondary endpoint. Exploratory objectives insclude correlating clinical outocmes with CD123 expression, determining CD123 expression in patients who relapsed after vibecotamab treatment, and to evaluate other immunological correlatives, including predictive molecular immune states, functional interrogation of T-cell receptor–antigen interactions, and nomination of leukemic neoantigens.

The study activated in May 2022 and is currently enrolllingpatinets at MD Andreson Cancer Center. As of May 2023, the study has enrolled 17 patients, 9 in the AML MRD+ cohort and 8 in the MDS/CMML cohort, out of a planned 20 patients per cohort. Enrollment is currently planned to be completed by the end of 2024.

“Vibecotamab... showed promising clinical activity in a phase 1study in relapsed/refractory AML,” the authors wrote. “Given promising activity of vibecotamab in low-blast AML, this phase 2 study is evaluating vibecotamab in other low-blast myeloid states.”

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REFERENCE

Short NJ, Bachireddy P, Huang X, et al. A phase II study of vibecotamab, a CD3-CD123 bispecific T-cell engaging antibody, for MRD-positive AML and MDS after hypomethylating agent failure. Presented at: ASCO 2023 Annual Meeting; June 2-6; Chicago, Illinois. Poster #BD204B