First Clinical Trial of Actimab-A Triplet Combination to Begin in AML

A clinical trial will evaluate the safety, optimal dosing, and rate and duration of complete remission of Actimab-A in combination with venetoclax and ASTX-727 in the frontline setting for patients with acute myeloid leukemia (AML), according to a press release from Actinium Pharmaceuticals, Inc.

This is the first clinical trial of Actimab-A under Actinium’s Cooperative Research and Development Agreement with the National Cancer Institute. Actimab-A, a humanized anti-CD33 antibody conjugated to actinium-225 that targets CD33, has shown tolerability and a manageable safety profile in combination with venetoclax in a phase 1 trial.¹ The combination also yielded an overall response rate (ORR) of 67%, a 1-year overall survival (OS) of 53%, and a 2-year OS of 32%.² At the recommended phase 2 dose, the ORR was 83%, and the measurable residual disease rate was 75%.²

Venetoclax in combination with hypomethylating agents (HMAs) is currently approved for patients with newly diagnosed AML.¹

“While Ven-HMA has positively impacted outcomes in AML, a significant number of patients have poor responses or relapse quickly resulting in dismal outcomes. We believe Actimab-A’s potentially synergistic, and mutation agnostic mechanism of action can improve clinical outcomes for these patients by producing deeper remissions, including measurable residual disease negativity, that are more durable,” said Avinash Desai, MD, chief medical officer of Actinium, in the press release.¹

Actimab-A’s mutation agonistic mechanism allows the antibody to overcome high-risk features such as TP53 mutations, Dr. Desai added.¹

“This triplet regimen can be conveniently administered in the outpatient setting as Venetoclax and ASTX-727 are both oral agents and Actimab-A does not require isolation given that it is an alpha-particle emitter,” he explained in the press release.¹

References

1. Actinium Pharmaceuticals announces initiation of Actimab-A triplet combination frontline trial under NCI CRADA with venetoclax and Taiho Oncology’s hypomethylating agent ASTX-727 in patients with newly diagnosed AML. PR Newswire. March 11, 2025. Accessed March 12, 2025. https://www.prnewswire.com/news-releases/actinium-pharmaceuticals-announces-initiation-of-actimab-a-triplet-combination-frontline-trial-under-nci-crada-with-venetoclax-and-taiho-oncologys-hypomethylating-agent-astx-727-in-patients-with-newly-diagnosed-aml-302397827.html
2. Actimab-A. Actinium Pharmaceuticals. Accessed March 12, 2025. https://www.actiniumpharma.com/product-pipeline/actimab-a