Actimab-A + CLAG-M demonstrates 100% remission rate in patients with R/R AML

On November 4, 2020, results were announced from a phase I trial evaluating actimab-A in combination with cladribine, cytarabine, filgrastim, and mitoxantrone (CLAG-M) in patients with relapsed and/or refractory (R/R) acute myeloid leukemia (AML). Of the evaluable patients in the third and planned final dose cohort, 100% achieved remission.¹

Actimab-A is an antibody–drug conjugate comprising the CD33-targeting monoclonal antibody, lintuzumab, and actinium-225. The agent was designed to selectively deliver actinium-225 to cancer cells, resulting in double-stranded DNA breaks and cell death.²

The actimab-A + CLAG-M combination regimen is being evaluated in patients aged ≥ 18 years who are deemed fit for cytotoxic chemotherapy. This phase I trial was preceded by the Investigational New Drug application clearance by the U.S. Food and Drug Administration (FDA) in 2018.

The novel combination was administered across three cohorts (N = 15) receiving distinct doses of actimab-A (0.25, 0.50, and 0.75 uCi/kg) with the standard regimen of CLAG-M. Across the treatment cohorts, 67% of patients achieved a complete remission (CR) or CR with inadequate hematopoietic recovery (CRi), and 83% of patients who had received ≤ 3 prior lines of therapy achieved CR or CRi. Of the patients achieving CR/CRi, 70% were measurable residual disease (MRD) negative. Data from all three cohorts, including those employing subtherapeutic doses of actimab-A, indicate the superiority of the combination over CLAG-M alone (overall response rate: 55%; MRD negativity: 39%). In the 0.75 uCi/kg actimab-A dose cohort, 100% of evaluable patients (n = 3) achieved CR/CRi.¹

The planned final dose of actimab-A (0.75 uCi/kg) in combination with CLAG-M demonstrated a clinically acceptable safety profile. As a result, patients are currently being screened and enrolled to evaluate a fourth dose of 1.0 uCi/kg actimab-A.¹

Data from this phase I study will be presented at the 62^nd American Society of Hematology (ASH) Annual Meeting and Exposition, which will be held virtually on December 5–8, 2020.