Promising Data Presented on Novel Radiotherapy for AML, MDS, Myeloid Malignancies

Encouraging new data show lintuzumab-Ac-225 (Actimab-A) to be a promising treatment backbone for relapsed or refractory acute myeloid leukemia (AML), Actinium Pharmaceuticals, Inc., reports in a press release. These data on combinations that incorporate this new radiotherapy were presented at the American Association for Cancer Research (AACR) Annual Meeting in Chicago, Illinois, in April 2025.¹

Lintuzumab-Ac-225 is a CD33-targeting radiotherapy that hones a powerful alpha-emitter radioisotope, actinium-225, for antileukemic effect. It is Actinium Pharmaceuticals’ lead product candidate and in development for management of AML, myelodysplastic syndromes (MDS), and other myeloid malignancies.¹

Regarding the radiotherapy’s performance in past AML clinical trials, Actinium Pharmaceuticals chair and chief executive officer Sandesh Seth commented in a press release that “Actimab-A has demonstrated potent single agent activity, synergy with other therapeutic modalities and efficacy in patients with high-risk features such as a TP53 mutation.”¹

The data presented at the AACR Annual Meeting were from preclinical models in which lintuzumab-Ac-225 was combined with standard-of-care targeted therapies for relapsed and refractory AML: azacitidine, the FLT3 inhibitors gilteritinib and quizartinib, and the KMT2A inhibitors revumenib and ziftomenib. The results showed a significant antileukemic effect of these combinations against AML cell lines that featured FLT3, KMT2A, NPM1, and TP53 mutations.²

“The data presented at AACR further support Actimab-A’s mutation agnostic mechanism of action across several of the most commonly expressed mutations and synergy with the targeted therapies approved for patients with these mutations,” Seth elaborated in the press release.¹

Clinical trial work on use of lintuzumab-Ac-225 within polytherapy approaches for AML continues, including in a phase 2/3 trial in which the radiotherapy will be combined with the CLAG-M (cladribine, high-dose cytarabine, granulocyte colony-stimulating factor, and dose-escalated mitoxantrone) chemotherapy regimen for relapsed or refractory disease. Another trial, to take place under a Cooperative Research and Development Agreement between Actinium Pharmaceuticals and the National Cancer Institute, will evaluate triplet therapy consisting of lintuzumab-Ac-225 plus venetoclax and the novel oral hypomethylating agent ASTX-727 for frontline AML management. Prior clinical results of treatment with lintuzumab-Ac-225 for high-risk relapsed and refractory disease have also been positive, including findings in patients with prior venetoclax treatment or bone marrow transplant.¹

Reference

1. Actinium Pharmaceuticals, Inc. Accessed May 8, 2025. https://ir.actiniumpharma.com/press-releases/detail/501
2. Chin AS, et al. American Association for Cancer Research Annual Meeting 2025. Abstract nr 594. https://doi.org/10.1158/1538-7445.AM2025-594