The publication highlights data including long-term survival outcomes from two-year follow-up and better outcomes in high-risk patients. Actimab-A is a novel targeted radiotherapeutic that uses the Actinium-225 (Ac-225) isotope payload directed against CD33, a marker expressed ubiquitously on AML blasts. The trial was conducted at the Medical College of Wisconsin (MCW) which has extensive experience treating relapsed refractory AML patients with CLAG-M.
Actimab-A + CLAG-M Trial Data Highlights from Publication:
18.4 month median Overall Survival (OS) in patients who received 1 or 2 lines of prior therapy
52% of patients in the Actimab-A +CLAG-M trial had TP53 mutations, 56% had prior allogeneic stem cell transplant and 56% of patients had prior Venetoclax therapy
Actimab-A + CLAG-M outcomes compare favorably to the results from historical data with CLAG-M alone in the pre-Venetoclax era from MCW's study (median OS of 13.3 months). Typically, patients who have failed Venetoclax treatment demonstrate median survival between 2.4 – 4.6 months as reported in the literature and the patients with a TP53 mutation even have more dismal survival outcomes. Hence this data supports the use of Actimab-A plus CLAG-M for these patients.
Actimab-A + CLAG-M produced high rates of measurable residual disease negativity (MRD-) including 75% across all patients, 83.3% in patients with a TP53 mutation and 100% in patients with prior Venetoclax therapy
71% of eligible patients received a bone marrow transplant (BMT) and median OS in these patients was 24.05 months
Dr. Sameem Abedin, Associate Professor of Medicine at the Medical College of Wisconsin and Principal Investigator of the Actimab-A + CLAG-M study said, "We are delighted that the Actimab-A + CLAG-M results have been published in the peer-reviewed journal Leukemia. Despite advancements in treatment, patients with r/r AML, particularly those with high-risk features including TP53 mutations and prior Venetoclax therapy like those in our study, continue to have dismal outcomes and limited treatment options.
We are excited that the combination of Actimab-A and CLAG-M produced high response rates with deep remissions including high rates of MRD negativity, improving access to potentially curable BMT resulting in enhanced survival outcomes. Importantly, we observed that responses were retained in high-risk patients. We believe these results support the utility of targeted radiotherapy for the treatment of AML and its mutation agnostic mechanism of action. We look forward to the initiation of the Phase 2/3 trial of Actimab-A + CLAG-M and further advancing this potentially important therapeutic modality in this patient population with a high unmet need."
Actinium has aligned with the FDA on a pivotal Phase 2/3 operationally seamless trial that will study Actimab-A + CLAG-M in r/r AML patients. The trial will optimize the dose of Actimab-A in combination with CLAG-M, that will be studied in the Phase 3 portion of the trial, which will be a randomized trial comparing overall survival and other outcomes of patients with r/r AML receiving Actimab-A + CLAG-M to CLAG-M alone. The trial is expected to be initiated in 2025.
Sandesh Seth, Actinium's Chairman and CEO, said, "There is significant momentum for Actimab-A with the publication of these positive results in Leukemia and the recent initiation of the frontline AML triplet combination with Venetoclax and the hypomethylating agent ASTX-727 under our NCI CRADA. Actinium is committed to addressing the needs of the over 100,000 patients with AML and MDS in the U.S. and Europe with Actimab-A to realize its multi-billion-dollar market opportunity. Over the course of 2025, we expect to generate additional clinical data further supporting Actimab-A's mutation agnostic, backbone therapy potential for radiation sensitive myeloid malignancies."
About Actinium Pharmaceuticals, Inc.
Actinium is a pioneer in the development of targeted radiotherapies intended to meaningfully improve patient outcomes. Actinium is advancing its lead product candidate Actimab-A, a CD33 targeting therapeutic, as potential backbone therapy in acute myeloid leukemia (AML) and other myeloid malignancies leveraging the mutation agnostic alpha-emitter radioisotope payload Actinium-225 (Ac-225). Actimab-A has demonstrated potential activity in relapsed and refractory acute myeloid leukemia (r/r AML) patients in combination with the chemotherapy CLAG-M including high rates of Complete Remissions (CR) including measurable residual disease (MRD) negativity with improved survival outcomes and is being advanced to a pivotal Phase 2/3 trial. In addition, Actinium is engaged with the National Cancer Institute (NCI) under the Cooperative Research and Development Agreement (CRADA) for development of Actimab-A in AML and other myeloid malignancies. The first clinical trial under the CRADA will evaluate the triplet combination comprised of Actimab-A, Venetoclax (Abbvie/Roche) an oral Bcl-2 inhibitor and ASTX-727 (Taiho Oncology, an Otsuka holdings company) a novel oral hypomethylating agent (HMA) in frontline acute myeloid leukemia (AML) patients. Iomab-ACT, Actinium's next generation conditioning candidate, is being developed with the goal of improving patient access and outcomes for potentially curative cell and gene therapies. Iomab-B is an induction and conditioning agent prior to bone marrow transplant in patients with r/r AML, which Actinium is seeking a potential strategic partner for in the U.S. In addition, the company's R&D efforts are primarily focused on advancing several preclinical programs for solid tumor indications. Actinium holds 230 patents and patent applications including several patents related to the manufacture of the isotope Ac-225 in a cyclotron.
For more information, please visit: https://www.actiniumpharma.com/
